In this update, we track the progress of COVID-19 vaccines and therapeutics as new clinical data and virus variants emerge.
Since we shared our perspectives on COVID-19-vaccine development in July 2020, the pandemic has grown in proportion across most of Europe and North America, with more than a million new cases every two days, and more than 10,000 deaths per day. Even communities that managed to flatten the curve in the spring and summer of 2020 found themselves backsliding in the fall. The loss of lives and livelihoods has been devastating—and that isn’t over yet—but there are some reasons to be cautiously optimistic about global recovery, not the least of which is the progress made to date on the pursuit of vaccines and other treatments for the novel coronavirus (SARS-CoV-2).
At least six vaccine manufacturers and two antibody-medicine manufacturers have shared preliminary results on the efficacy of their products—data that have outperformed the initial expectations of most experts. Already, the first vaccinations have been administered in more than 50 countries, including Brazil, Canada, China, India, Israel, Russia, the United Arab Emirates, the United Kingdom, most countries in western Europe, and the United States. Such progress has instilled hope in many that vaccines may, indeed, “save the world.”
But while COVID-19 vaccines will almost certainly be one of the most critical tools for moving the world toward an epidemiological end to the pandemic, they will likely not be the only ones: diagnostics, antibody medicines, and other therapeutics will be important complements. A lot of work must also be done to ensure sufficient vaccination coverage for communities to reach herd immunity. “Sufficient” coverage would be between 60 and 70 percent of the population, although the figures are now possibly higher, given the emergence of new, more easily transmitted variants of SARS-CoV-2.1
In this article, we review the initial results from clinical trials of COVID-19 vaccines and explore several remaining uncertainties that are relevant to stakeholders across the globe: How many doses will we have and by when? How will the logistics work for distribution and administration? And, critically, will consumers agree to be vaccinated?
While COVID-19 vaccines will be critical tools for an end to the pandemic, diagnostics, antibody medicines, and other therapeutics will be important complements.
Initial data from clinical trials
COVID-19-vaccine candidates from BioNTech and Pfizer (in partnership) and from Moderna have demonstrated a rate of about 95 percent protection from infection with symptoms after two doses are administered several weeks apart.2 Additionally, a vaccine candidate from AstraZeneca has demonstrated a range of efficacy that depends on the trial protocol: 90 percent for a half plus a full dose, 62 percent for two full doses, and 82 percent for two full doses with a longer interval between them.3 Recent reports from Johnson & Johnson and Novavax have also been encouraging. Johnson & Johnson demonstrated that its single-dose vaccine confers 66 percent immunity against infection in a multiregion, multivariant data set, with 72 percent efficacy in the United States, 57 percent in South Africa, and 66 percent in Latin America. It also demonstrated 85 percent (28 days) and 100 percent (49 days) efficacy against severe disease.4 A vaccine candidate from Novavax demonstrated efficacy of 89 percent in a UK trial and 49 percent in a South Africa trial5 (Exhibit 1).
Specific ranges of efficacy vary among these vaccine candidates, but each has demonstrated an efficacy of at least 85 percent against severe disease.
This is all good news for several reasons: individuals will benefit from the health protection offered by the vaccine, the positive outcomes may encourage others to get vaccinated, and the proportion of the population required to reach herd immunity may be reduced.
It’s increasingly probable that multiple COVID-19 vaccines will be available in the coming months. Among others, CureVac, GlaxoSmithKline and Medicago (in partnership), and Inovio all have COVID-19-vaccine candidates in late-stage development (Exhibit 2). Several COVID-19-vaccine candidates from China, India, and Russia are also in late-stage development. For instance, in an interim analysis of data from a Phase III trial reported in The Lancet, the Sputnik V vaccine from the Gamaleya National Center of Epidemiology and Microbiology showed overall efficacy of 92 percent.6
None of the leading COVID-19 vaccine candidates reported serious side effects during clinical trials, but additional safety data are being collected, as required by regulatory guidelines for licensure. For example, during the initial rollouts in the United Kingdom, the United States, and other markets of the COVID-19 vaccines from Moderna and Pfizer–BioNTech, there were some rare reports of anaphylaxis (2.1 cases per million and 6.2 cases per million, respectively, based on preliminary data), which led regulators to recommend that any person with a history of anaphylaxis related to food, a medicine, or a vaccine not receive the two COVID-19 vaccines.7
Additionally, it remains to be seen how long the protection from COVID-19 achieved by the vaccines will last. And because the trials haven’t yet included children, it isn’t known whether the efficacy will be comparable in those younger than the age of 18 years. More information will be revealed as the sample size grows and an increasingly diverse population is inoculated.
There has also been progress on the development of therapeutics for COVID-19. In November 2020, for instance, Eli Lilly’s antibody medicine bamlanivimab was granted Emergency Use Authorization (EUA) by the US Food and Drug Administration. In clinical trials, it had demonstrated a 72 percent reduction in the rate of hospitalizations and emergency-department visits.8 Additionally, Regeneron Pharmaceuticals submitted its antibody cocktail REGN-COV2 for EUA in October 2020. In trials, the therapy had demonstrated a tenfold reduction in viral load, on average, and a 57 percent reduction in COVID-19-related medical visits.9 Those and other antibody medicines in development are part of a growing assortment of treatments and protocols related to COVID-19 that, collectively, could reduce mortality among hospitalized patients by between 18 and 30 percent.10
Additionally, it will be important to monitor the efficacy of vaccines and therapeutics against new variants of SARS-CoV-2 that have been identified in Brazil, South Africa, the United Kingdom, and other regions and that have in some geographies become the predominant strain. Multiple COVID-19 vaccines have demonstrated immune response to variant B.1.1.7, which was first identified in the United Kingdom. However, the B.1.351 variant, which was first identified in South Africa, has generated more concern in the scientific community; preliminary lab and clinical data across multiple vaccine candidates suggest that efficacy against this strain could be lower. Multiple vaccine manufacturers have reported preliminary data showing a severalfold reduction in antibody neutralization potency against the B.1.351 variant and relatively lower vaccine efficacy in trials taking place in South Africa—for example, 50 to 60 percent efficacy in South Africa trial data versus 70 to 90 percent efficacy in trial data in regions where B.1.351 is not predominant.11 This variant has also demonstrated evasion from the antibodies generated by natural infection (which are present in convalescent sera) and monoclonal-antibody therapies, suggesting the possibility of reinfection and limited effectiveness of the therapeutics currently available.12
It’s becoming increasingly clear that COVID-19 vaccines will play a crucial role in controlling the pandemic. As vaccines’ role in saving the world expands, the baton passes from vaccine manufacturers to governments and local jurisdictions to assess what else will be required to move from having an approved vaccine to completing large-scale inoculation. Through research and conversations with healthcare experts in the field, McKinsey has identified several critical elements of an effective vaccination program as well as some of the remaining uncertainties associated with each (Exhibit 3).
Specifically, vaccines and the mechanisms for administering them must include the following features:
- Available. Will there be enough of the vaccine to inoculate the world and reach herd immunity?
- Administrable. Who will get the vaccine first, and where will it be available?
- Accessible. How will the logistics of the vaccine be managed, particularly if it has complex, cold-chain requirements?
- Acceptable. Will consumers (especially those at highest risk of contracting a severe form of the disease) have trust and conviction to get vaccinated?
- Accountable. What would a closed-loop surveillance system look like to build more confidence in the long-term safety of the vaccine?
Questions about availability and capacity are front of mind for many who have been facing direct and indirect health risks and economic shock related to the COVID-19 pandemic. The foresight (and urgency) shown by the biopharmaceutical industry, major donors, multilateral organizations, and governments allowed innovators to scale up the manufacturing capacity for COVID-19-vaccine candidates even before much was known about their safety and efficacy. The potential outcomes of those at-risk investments are now beginning to come into focus.
Will there be enough of the COVID-19 vaccines for the world?
If all COVID-19-vaccine innovators are successful in clinical trials, and if manufacturing commitments to scale up hold true, there may be enough capacity to vaccinate nearly 80 percent of the global population against COVID-19. According to manufacturers’ public announcements, more than 14 billion doses’ worth of capacity (including 2020 capacity) is planned for 2021 (Exhibit 4). Assuming that all innovators’ vaccines are successful and require two doses (dosing remains uncertain for some of the vaccine candidates), full COVID-19-vaccine courses could be available for six billion individuals—approximately the size of the entire global adult population.
It may not be realistic to assume that every COVID-19-vaccine candidate will succeed. Some haven’t made it through clinical trials to the level of EUA; others still need to collect more data for Biologics License Application reviews in the first and second quarters of 2021. The vaccine manufacturers’ capacity estimates may also be over- or understated, depending on whether in-process or planned increases were reported.
Global scale-up of the manufacturing capacity for COVID-19 vaccines will likely occur over the course of 2021. The details are still emerging, but innovators’ estimates suggest that manufacturing capacity will ramp up over the course of 2021. In the first half of 2021, the United States is likely to have around 500 million doses of the Johnson & Johnson, Moderna, and Pfizer–BioNTech vaccines, based on the reported delivery deadlines.13
Given the contracted volume from those manufacturers, there will be sufficient vaccine doses available in the United States by the end of May for at least 300 million people—enough doses to immunize 100 percent of the adult population (Exhibit 5). AstraZeneca announced it will have enough capacity to produce 700 million doses of its COVID-19 vaccine for global distribution in the first quarter of 2021 and the remainder of its three billion doses later in the year.14
Depending on the success of COVID-19-vaccine candidates in late-stage development, the range of capacity scenarios may change. As mentioned previously, it’s unlikely that all the vaccine candidates will be successful. Some developers have already experienced setbacks (for example, the need to reformulate vaccines for certain populations) during late stages that have delayed their vaccine-development timelines. But even if we assume that only a few candidates will succeed and see broad uptake (for example, those vaccines that are currently authorized for emergency use or under review by the EU European Medicines Agency and the US Food and Drug Administration), there would be capacity to manufacture between 5 billion and 6 billion doses in 2021—enough to inoculate approximately 40 percent of the global population.
Moreover, if we assume the ultimate success of all vaccines currently authorized or under review in at least one geography, there should be capacity to manufacture approximately 12 billion doses of COVID-19 vaccines by the end of 2021—enough to vaccinate 85 percent of the global population.
There may be sufficient manufacturing capacity for global COVID-19-vaccine coverage, but individual countries’ contracted doses vary significantly. Most of the global capacity for COVID-19-vaccine manufacturing (more than seven billion doses) has been contracted and reserved by individual governments and institutions, although COVAX recently announced that it had arrangements in place to access nearly two billion doses of COVID-19-vaccine candidates on behalf of 190 participating economies (Exhibit 6). Country-specific agreements vary significantly, depending on the region and the relative size of population.15
In fact, it’s possible that a significant number of countries—particularly those with wealthier economies—have contracted doses that exceed the needs of their populations. We haven’t even accounted for the possibility that some countries won’t vaccinate recovered patients or that not every targeted citizen will choose to receive a vaccination. Government leaders must consider how to manage the excess doses that will likely be available around the middle of 2021 to address the global challenge.
What other challenges remain?
Even as questions about COVID-19-vaccine availability and capacity become more clear, it will be critical in the coming months to monitor progress in other areas of vaccine development. Global attention is already shifting to the challenges associated with vaccine rollout and consumer adoption. Other underlying questions will also need to be addressed in the background, including those related to long-term safety, duration of protection, efficacy after the first dose of a multidose course (recent data show that some COVID-19 vaccines may be somewhat effective after only one dose16), impact of the vaccine on transmission of the virus, and efficacy in specific patient populations, including the pediatric population. To reach the ideal vaccine profile—that is, a single dose with an impeccable record of long-term safety, extended duration of protection (ideally, five years or longer), and high efficacy against the disease—it will be critical for developers and other key stakeholders to make progress in several areas.
Realizing a pipeline of COVID-19 vaccines
The early success of the first few COVID-19-vaccine candidates is exciting, but the world will likely need additional, next-generation candidates in the pipeline to provide additional capacity. The vaccines that may become part of endemic vaccination in a country’s schedule may need to optimize for the other parameters (for example, dosing and duration of protection) as much as—or perhaps more than—they do for efficacy.
Shifting the paradigm of COVID-19-vaccine development
It will become difficult to recruit patients for clinical trials of the next generation of COVID-19 vaccines once the current vaccines with EUA are rolled out. Even if COVID-19 vaccines aren’t available for everyone immediately, some segments of the population are likely to wait a few weeks or months to get a vaccine that demonstrates 95 percent efficacy rather than enroll in a trial with a 25 to 50 percent chance of them receiving a placebo (or a 50 to 75 percent chance of them receiving a vaccine of uncertain efficacy).
For future COVID-19-vaccine candidates, ethics guidelines may also recommend a head-to-head comparison with existing vaccines, which would make clinical trials operationally challenging, requiring hundreds of thousands (if not millions) of patients to reach efficacy endpoints comparable to a vaccine with 95 percent efficacy. Regulators will need to think through that dilemma in short order and provide guidance in the absence of defined correlates of protection.
Monitoring and adapting to emergent SARS-CoV-2 variants
Key COVID-19-vaccine stakeholders will need to continue to monitor and adapt to the new SARS-CoV-2 variants emerging across the globe to respond effectively. COVID-19-vaccine manufacturers should continue to rapidly test (for example, in nonclinical assays and animal models) the effectiveness of their vaccines in provoking an immune response to new variants. Manufacturers have already announced new development plans in response to emerging variants. These include booster doses, new stand-alone vaccines matched to the new variants, and multivalent vaccines designed to confer immunity to multiple strains in one product.
For governments, health systems, and other stakeholders involved in immunization, the potential proliferation of vaccine products in response to new strains would create more complexity across the value chain (for instance, in procurement, administration, and manufacturing-capacity management).
Freeing up the production capacities and supply chains related to COVID-19 vaccines
Some COVID-19-vaccine manufacturers have aggressively partnered to ramp up their production capacities across geographies. Technology transfer at the required scale and in such a compressed time frame is complicated, and it’s far from a done deal that it will work as intended. Governments, manufacturers, nongovernmental organizations, and others will need to deploy creative solutions to resolve issues or bottlenecks—for instance, by creating a knowledge-management infrastructure and applying digital tools and advanced analytics to technology transfers. Indeed, given the requirements of several of the COVID-19 vaccines, supply chains will likely present some challenges for manufacturers in low- and middle-income countries. The infrastructure may not allow for large-scale distribution of a vaccine that requires the long-term, complex, cold-chain storage required by some mRNA vaccines.
Addressing the uncertainties about COVID-19 vaccination
Even if the R&D and supply-chain challenges related to COVID-19 vaccines are resolved, the impact of the vaccines on the course of the pandemic is contingent upon equitable consumer access and adoption. Consumer-sentiment surveys in the United States show that around 100 million Americans don’t sufficiently trust the vaccine-development process and are uncertain or ambivalent about getting vaccinated in the first six months following initial availability. To put the world on a path to societal and economic recovery, it will be critical to have public- and private-sector support for at-scale COVID-19-vaccine adoption.
There’s clearly lots to cheer about when it comes to COVID-19-vaccine development, but there is just as much to ponder as the situation evolves. In the face of continuing ambiguity, it’s important for all participants in the healthcare ecosystem to provide scientific and regulatory environments that will allow the further development of the vaccine pipeline; effective technology transfer, manufacturing, logistics, and distribution; and increased and equitable uptake by consumers. They all remain daunting challenges for the largest-ever public-health intervention in history.
Innovators are sprinting to develop inoculations against the novel coronavirus. Here, we summarize the latest information on research timelines and the potential impact of a vaccine on the pandemic—and society.
When the novel coronavirus (SARS-CoV-2) emerged in late 2019 and began its spread around the world, the global innovation community mobilized quickly to initiate the development of a vaccine for COVID-19, the disease it causes. Hundreds of individuals and institutions—in academia, biotechnology, government, and pharmaceuticals—embarked on one of the most consequential scientific endeavors in living memory. Funding poured in from governments, multilateral agencies, not-for-profit institutions, and the private sector. Regulators showed uncanny speed in working with innovators. Now, months later, more than 250 vaccine candidates are being pursued globally, with 30 already in clinical studies and another 25 or so poised to enter human trials in 2020.
As the novel coronavirus continues to spread (with roughly 1.5 million new cases of COVID-19 globally each week) and the pursuit of a vaccine intensifies, debate has grown among corporate leaders, economists, public-policy makers, and scientific experts—and even in our own living rooms. Will we have a COVID-19 vaccine? If so, when? And how much value can it provide to society?
To bring more clarity to the conversation, we conducted an in-depth review of the COVID-19-vaccine pipeline and the range of potential immunization and demand scenarios. We looked at publicly available information on the potential time to develop COVID-19 vaccine candidates compared to other vaccines, as well as potential barriers. We spoke with experts in epidemiology and public health, as well as important participants in the vaccine ecosystem (among them, developers, funders, and government organizations). We synthesize that body of research and analysis in this article. Our goal wasn’t to judge whether vaccine development should be accelerated or not; ensuring that safety protocols are being followed and outcomes are being rigorously monitored is of the utmost importance.
Here is what we found:
- Vaccine developers and government officials are publicly reporting timelines for potential emergency use of vaccine candidates between the fourth quarter of 2020 and the first quarter of 2021.
- The early data on vaccine safety and immunogenicity in Phase I and II trials are promising—although in a limited number of subjects to date.
- The discrete characteristics of the virus, the sheer number of development efforts, and innovators’ unprecedented access to funding all provide reasons to believe that a COVID-19 vaccine can be developed faster than any other vaccine in history. (It took four years to develop the mumps vaccine, which was previously the fastest developed novel vaccine.17) More than 50 candidates are expected to enter human trials in 2020, and 250 total vaccine candidates are being pursued. Historical attrition rates would suggest that such a pipeline could yield more than seven approved products over the next few years.
- A number of hurdles remain, including validating unproven platform technologies, demonstrating vaccine candidates’ safety and protection against COVID-19, and delivering the highest-impact vaccine profiles.
- Regulatory bodies are still finalizing guidelines for COVID-19 vaccines. Recent guidance from the US Food and Drug Administration (FDA), for example, suggests the need for more data prior to granting Emergency Use Authorizations (EUAs). Details are still being worked out.
- Vaccine manufacturers have announced cumulative capacity that could produce as many as one billion doses by the end of 2020 and nine billion doses by the end of 2021.
Taken together, all the evidence suggests that COVID-19 vaccines are likely to become available for focused populations somewhere between the fourth quarter of 2020 and the first quarter of 2021. The ultimate role they will play in the world’s response to the pandemic will depend on a range of factors—for instance, the disease’s epidemiology and transmission, the duration of immunity from natural infection, the profile of vaccines, and the availability of complementary therapeutics and diagnostics. It’s assumed, however, that vaccines will play an important role in most response scenarios and may “save the world” in worse scenarios. In all scenarios, vaccines will serve as an insurance policy against continued health and economic shocks from the pandemic.18
What isn’t up for debate is that business leaders, governments, and policy makers will need to continually monitor and respond to those exogenous factors.
Depending on their roles, participants in the vaccine ecosystem must be prepared to focus on some combination of the following six critical actions: adapt to a range of demand scenarios; ensure that manufacturing is flexible and fungible; understand that multiple vaccines may play different roles over time; collaborate with others to drive vaccine delivery, adoption, and monitoring; prepare now to support uptake of a vaccine; and consider endemic and postpandemic time horizons when making decisions.
Focusing on those tasks today can help stakeholders build the capacity and response system required to address not just the COVID-19 pandemic but also any future pandemics.
A question of timing: Will we have a vaccine, and if so, when?
Developers are under an unprecedented level of scrutiny as they move their vaccine candidates into clinical trials—not so surprising when you consider how many experts have tied the availability of a COVID-19 vaccine to the world’s return to “a semblance of previous normality.”19 Experts have proposed a range of potential timelines, with some speculating that a vaccine will be available by the end of 2020 and others arguing it may take 12 months longer, at least, to bring a COVID-19 vaccine to market. What follows is an overview of publicly available evidence of vaccine timelines, promising early evidence from Phase I and II clinical trials, and several other virus-specific and innovation-related development factors.
Developers’ and government officials’ publicly available timelines
Given the sheer number of potential COVID-19 vaccines in development and the public statements from several developers, it seems likely that one will be available in the United States between the fourth quarter of 2020 and the first quarter of 2021, with more following throughout the year—potentially granted under the FDA’s EUA guidelines.20 Under that authority, the FDA “may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN [chemical, biological, radiological, and nuclear] threat agents when there are no adequate, approved, and available alternatives.” Similar approvals are being sought by companies in China and Europe: at least five large vaccine developers have announced that they intend to submit applications for EUA, or the local equivalent, for their candidates before the end of 2020 (Exhibit 1).
Government officials have also publicly stated that a vaccine could be approved by the end of 2020 or early in 2021. As Dr. Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, recently said, “… by the end of this calendar year and the beginning of 2021, I feel optimistic. Nobody guarantees, but I feel optimistic that we will have a vaccine, one or more, that we can start distributing to people.”21
Early evidence from Phase I and II clinical trials
Several companies have released data from Phase I and Phase II clinical trials that are promising:
- In June, Sinovac Biotech released preliminary results from a Phase I/II trial of its candidate, citing the induction of neutralizing antibodies in more than 90 percent of people who were tested 14 days after receiving two injections two weeks apart, with no severe adverse events reported.22 China National Pharmaceutical (known as Sinopharm) presented interim readouts from a Phase I/II trial of its candidate in the same month, claiming that 100 percent of participants who received two doses over 28 days developed neutralizing antibodies.23
- In early July, Pfizer and BioNTech published preliminary results from a Phase I clinical trial of their candidate, indicating that “geometric mean neutralizing titers reached 1.8- to 2.8-fold that of a panel of COVID-19 convalescent human sera.”24 In that same time frame, Moderna published interim data from a Phase I trial of its vaccine candidate, demonstrating that 41 of 41 vaccinated participants developed neutralizing antibody titers using both a live virus and a pseudovirus assay. Across dose levels, titers were either comparable to or above those seen in a panel of convalescent sera. The geometric mean titers post-boost at the 100 microgram dose were between 2.1- and 4.1-fold higher than those seen in convalescent sera.25
- In mid-July, AstraZeneca published interim data from a Phase I/II trial of its vaccine candidate, indicating that a single dose resulted in a fourfold increase in antibodies in 95 percent of participants one month after injection.26 Also in that time frame, CanSino Biologics published interim Phase II data for its vaccine candidate, demonstrating that a single dose induced antibodies in more than 85 percent of participants and a T-cell response within 14 days of receiving the vaccine.27
Further data on those and other vaccine candidates are needed, but initial results point to the idea that candidates are developing neutralizing antibodies to some degree—a potential indicator of efficacy.
Reasons to believe in accelerated development of a COVID-19 vaccine
A closer look at three key development factors—the novel coronavirus’s underlying characteristics, the unprecedented size of the vaccine pipeline and number of technology platforms being used, and greater access to funding—points to the potential for the accelerated development and approval of a COVID-19 vaccine, faster than any other vaccine in history.
Unlike some families of viruses, such as HIV and the one related to seasonal influenza, coronaviruses overall have been shown to mutate at relatively low to moderate rates. The MERS-causing coronavirus, for instance, hasn’t mutated substantially since it was detected in the population in 2012.28 In fact, early data suggest that the novel coronavirus is mutating at a rate four times slower than that of the virus causing seasonal influenza.29 Some evidence is emerging that mutations are affecting the transmission of COVID-19, but so far these appear to have had a minimal effect on antigenicity.30 Such mutation patterns are advantageous for vaccine developers, as they alleviate the complexities associated with designing a vaccine for a moving target. Speed is of the essence, of course: all viruses always have the potential to mutate and evolve, particularly the longer they are in circulation in the population.
The sustained attack rate of the disease may allow developers to assess vaccine efficacy rapidly in Phase III. Some developers are seeking to conduct clinical trials of their COVID-19-vaccine candidates in those regions that have seen recent upticks in infection rates, such as Brazil, India, and parts of the United States, including Arizona, Florida, and Texas.31
Pipeline and technology platforms
There has been unprecedented activity around the development of a COVID-19 vaccine. The first vaccine candidate was created 42 days after the genetic sequencing of the novel coronavirus. At the time of publication, there are more than 250 announced candidates globally, with more than 50 planned entries into human clinical trials in 2020 (Exhibit 2). What’s more, the candidates have incorporated a broad range of technologies, from proven vaccine platforms (such as protein-subunit and viral vectors) to novel ones (such as messenger RNA and DNA). Of the candidates that companies intend to enter into trials this year, more than 30 are already in human studies, according to data from clinical trial registries.
There has been unprecedented activity around the development of a COVID-19 vaccine. The first vaccine candidate was created 42 days after the genetic sequencing of the novel coronavirus.
To get a better sense of the likely number of successful candidates, we reviewed key development factors plus the historical probabilities of success in vaccine development. Our analysis, based on the existing pool of announced candidates, suggests that between seven and nine vaccines could obtain regulatory approval within the next two years. Under more optimistic scenarios, that number increases to more than 20 vaccines.
In our analysis, we accounted for differences in development timelines and in the platform technologies being used. If a vaccine candidate isn’t starting a clinical trial until 2021, for example, it may face funding or trial-recruitment challenges that could delay timelines. It may therefore have a lower likelihood of success. And vaccine candidates that are using novel technology platforms in their development may have a hard time succeeding if those platforms end up failing more broadly compared to other candidates (see sidebar, “Chances of success”).
Access to funding
COVID-19-specific vaccines have received more funding than any prior vaccine whether developed under business-as-usual or pandemic scenarios. Public records show that from 2003 to 2014, the US National Institute of Allergy and Infectious Diseases invested a total of $221 million in the development of an Ebola vaccine. By contrast, the institute received $1.5 billion in the first six months of 2020 to support efforts to develop a COVID-19 vaccine.32 Governments, nongovernmental organizations, and private companies are making similar monetary commitments, with a substantial portion of the funds being directed toward individual vaccine candidates.33 Our analysis suggests that global investment in COVID-19 vaccines to date has totaled at least $6.7 billion.
Potential hurdles to overcome
The breadth and depth of the pipeline for COVID-19-vaccine candidates and the unprecedented level of investment in their development suggest that a vaccine may be on the near-term horizon. But there are still challenges to overcome—three in particular, according to our research: validating unproven platform technologies, demonstrating protection against COVID-19, and targeting the appropriate vaccine design.
- Validating unproven platform technologies. Several of the technologies—for example, DNA and messenger RNA—being used to develop COVID-19-vaccine candidates hold unique advantages over traditional platforms, the chief one being their ability to accelerate development time.34 However, those platforms are largely unproven: there are no licensed vaccines for humans that have been approved using them. Questions remain regarding the long-term safety of the new modalities, as well as the degree to which they can induce a strong and lasting immunity response. As a result, they may face greater regulatory scrutiny compared with more established technology platforms.
Demonstrating protection against COVID-19. Before a COVID-19 vaccine reaches the market—through either emergency-use or full regulatory approval—its developer will of course need to demonstrate that the vaccine candidate confers protection against the disease. Regulators require such evidence so they can have confidence in the efficacy of a vaccine candidate and potentially give high-risk populations early access to it. Vaccine developers will need to establish a sufficient indicator of protection—for example, demonstrating that the candidate provokes a certain level of antibody response in immunized individuals and then separately showing that antibodies confer protection against viral infection for a certain window of time (through assays or animal-transfer models).
In addition, COVID-19-vaccine developers will need to design and conduct late-stage clinical trials in a way that enables them to demonstrate the full efficacy of their vaccine candidates rapidly. For instance, they may want to enrich site selection for clinical trials, targeting regions in which COVID-19 hasn’t had prior high attack rates (thus, with fewer exposed trial participants) but in which attack rates would rise after participants had been immunized. That way, they could rapidly assess the efficacy of the vaccine candidate being tested.
- Targeting the appropriate vaccine design. One of the outstanding questions for COVID-19-vaccine developers is to what degree the novel coronavirus will mutate around the spike protein, which latches onto cells and transmits the virus through cell membranes. While there has been limited significant mutation within the novel coronavirus to date, future changes to the spike protein itself could affect the relevance of the vaccine candidates currently in development, as most innovators have designed them around the spike protein. If mutations did occur and candidates needed to be revisited, it would obviously create delays for a successful vaccine launch.
Regulators have been contemplating the appropriate guidelines to assess all the evidence that will be arriving imminently on vaccine candidates. Before the end of 2020, a few innovators should have limited data sets for safety and immunogenicity. Given the low mortality rates for COVID-19 among the general population, it remains to be seen whether regulators will deem clinical trial data collected in 2020 sufficient for the deployment of the vaccine in certain high-risk populations. Recent guidelines by the FDA suggest that vaccine candidates will need more data to be granted EUA—but even that decision will likely depend on a number of factors, including how convincing the data are, how the pandemic evolves, and the risk–benefit assessment of the vaccine in a broader context.
To date, several manufacturers have announced capacity plans that total about one billion COVID-19 vaccine doses by the end of 2020 and eight billion to nine billion doses by the end of 2021 (Exhibit 3). Not all of their vaccines will be successful, of course, but this industry announcement is an encouraging sign that when candidates are approved there will be capacity to reach various patient populations now and over time.
In total, the evidence base suggests it is likely that some COVID-19-vaccine candidates will be available between the fourth quarter of 2020 and the beginning of 2021. The initial set of approved candidates is likely to be small, for use in specific patient groups, and supply may be constrained. Later in 2021, additional candidates on other technology platforms could receive approval and be manufactured on a broader scale and approved for broader populations.
A question of value: How will a vaccine affect society?
Another issue up for debate is the potential value of a COVID-19 vaccine to the global community. How important is a vaccine for overcoming the health-related effects of COVID-19 and its associated effects on the global economy? We attempt to contextualize the importance of vaccine-development efforts over three time horizons: near term, in the current COVID-19 pandemic; midterm to longer term, in which COVID-19 becomes endemic or requires revaccination (for example, because of waning protection or strain mutation); and longer term, looking at global-pandemic preparedness beyond the COVID-19 crisis (Exhibit 4).
In the near term, COVID-19 vaccines would prevent more people from becoming infected and dying. The second-order effects include controlled utilization of hospitals and healthcare resources, the development of herd immunity, and gradual economic recovery. In the midterm, if COVID-19 were to become endemic, the presence of a vaccine would allow the broader population to be inoculated (as with other standard immunizations, such as those for the seasonal flu and for measles, mumps, and rubella). And if the disease mutates or immunity is short lived, the additional development and manufacturing capacity currently being established could be applied quickly to increase vaccine supply, create new vaccines, and accelerate the response to future pandemics.
The profile of a valuable vaccine
In the near term, a COVID-19 vaccine’s value to society will be determined by four factors: the vaccine’s profile, the disease-attack rate, the duration of natural immunity, and complementary therapeutics and testing (Exhibit 5).
The most valuable COVID-19 vaccines will be the ones that can be administered once, have 100 percent effectiveness, and provide immunity for years. Of course, based on what we know about vaccine development historically, achieving that type of vaccine profile would be like finding the proverbial needle in a haystack. Developers face many challenges in getting to that perfect state. Vaccines must be able to be manufactured and distributed at sufficient scale. Limited supply could force policy makers into tough decisions about who receives a vaccine first. And onerous methods of vaccine distribution or administration—for instance, if they require cryoshipping or a complex delivery device—could limit usage rates in geographies that lack the necessary infrastructure.
The value of a COVID-19 vaccine will also be influenced by the disease’s rate of attack. If viral-transmission rates drop significantly, the need for a vaccine is obviated. If they accelerate, populations may achieve natural herd immunity and thus in most cases no longer require immunization. However, if the rates remain at current (moderate) levels, there will likely be an acute need for vaccines to control infection rates.
The length of natural immunity conferred to recovered individuals will be another critical determinant of a vaccine’s value. If the duration is in line with that of the vaccine for seasonal influenza, individuals who were infected and recovered in the first wave of the COVID-19 pandemic will still require vaccination to protect against future outbreaks.
Of course, if one of the more than 250 COVID-19 therapeutics currently in development prove particularly effective at treating the disease, there could actually be reduced demand for a vaccine. More widespread testing may lead to earlier identification of COVID-19-positive individuals, further dampening the transmission of the disease and allowing for early treatment to improve outcomes, thus reducing the burden on the healthcare system.
Near-term vaccine demand
Given all the value-determination factors, what could the overall near-term demand for COVID-19 vaccines look like? Our research reveals three potential scenarios for vaccine demand, all of which warrant consideration by government agencies, nongovernmental organizations, pharmaceutical companies, and vaccine manufacturers (Exhibit 6).
At one end of the spectrum, vaccines are viewed as critical components of the solution to the COVID-19 crisis. They serve as the primary countermeasure against COVID-19, driven by sustained, moderate viral-transmission rates; limited duration of immunity (either natural or vaccine induced); few effective therapeutics; and favorable product profiles.
In a more moderate scenario, vaccines have a focused role, with the demand still significant, albeit lower. For example, if transmission rates remain stable, the duration of immunity from a vaccine is about three to five years, and the availability of therapeutics and testing improve, the broad-scale need for vaccines is less acute. However, a COVID-19 vaccine could still be used to protect vulnerable populations (such as healthcare workers and immunocompromised patients) and to address hot spots that could emerge in future waves.
At the other end of the spectrum, in a scenario in which COVID-19 transmission wanes and breakthrough therapeutics against the disease emerge, a vaccine has a somewhat limited role, serving as more of an insurance policy for society. There would likely be more focused demand for a vaccine in this scenario (for example, for use in high-risk populations), but the investment made to develop and scale the COVID-19 vaccine would be considered protection from a more severe outbreak.
A question of preparedness
Clearly, there is momentum behind global innovators’ vaccine-development efforts. Experts agree there is a strong likelihood of a vaccine coming to market in the next six to 12 months, and an even stronger indication that an effective COVID-19 vaccine can create outsize value for global citizens, economies, and healthcare systems. With all that in mind, there are six actions that stakeholders in the vaccine ecosystem can take as they continue with development, manufacturing, policy making, implementation, and other efforts.
1. Adapt to a range of demand scenarios
As noted, a variety of scenarios can emerge that will affect the demand for a potential vaccine. Governments, distributors, manufacturers, regulators, and other stakeholders should build contingency plans to react and adapt successfully. Such plans should take into account the three scenarios cited earlier, the potential vaccine candidates that could be approved, and the corresponding distribution and access requirements of those vaccines.
2. Ensure that manufacturing is flexible and fungible
Vaccine innovators are already factoring manufacturing decisions into their development processes much earlier than they ever have. As noted, several manufacturers have announced capacity plans that total about one billion doses by the end of 2020 and eight billion to nine billion doses by the end of 2021. But the reality is that some candidates will fail and some capacity plans may be delayed.
Developers and funding partners need to build flexibility and fungibility into their manufacturing processes and networks. Companies should also plan for how they might redirect capacity—whether internal capacity or that gained through bilateral partnerships—to other promising vaccines. Developers must be open to new types of partnerships, even with competitors, in some cases. In addition to private-company manufacturing, public partnerships are emerging to increase manufacturing capacity and expand further the global access to a vaccine.35
3. Understand that multiple vaccines may play different roles over time
As we have noted, different vaccines will be available and scaled at different periods in the next six to 24 months. Experts agree we are unlikely to see a single vaccine, including the earliest ones, with all the ideal vaccine characteristics, so health officials, policy makers, and regulators will need to consider carefully the juxtaposition of the multiple vaccines they have in development and how they complement one another. For instance, a vaccine that is safe, has moderately high efficacy, and conveys several months of immunity could play an important role in allowing people to get back to work, thereby kick-starting a global economic recovery. Future vaccines with improved efficacy profiles may then complement vaccines that were approved earlier.
4. Collaborate to drive delivery, adoption, and monitoring
Innovators are experienced in designing, developing, testing, and manufacturing a safe and effective vaccine, but if the vaccine isn’t shipped, distributed, and administered in a thoughtful way, innovators’ efforts may be in vain. Multiple organizations are already working on frameworks to ensure global access to vaccines, which will be a top priority. In most demand scenarios, the speed and size of the vaccine rollout–potentially in the billions of doses–will be unprecedented. It will be important for stakeholders to take an end-to-end view of their roles; that is, from product shipment, to healthcare provider consultations, to vaccine administration.
Different vaccines have different logistical needs, including dosing schedules, site of administration, and cold-chain requirements. DNA-based vaccines, for instance, are traditionally shelf stable at normal temperatures, while RNA-based, protein subunit, and viral vectors require cold chain or cryoshipping. As with manufacturing, stakeholders should consider working with partners to develop logistical plans contingent upon the various demand scenarios. They should, for instance, consider how individuals will receive the vaccine and what other efforts that may entail—for example, can it be administered in a retail setting by a nurse practitioner or only in a physician’s office?
Providers and other stakeholders should also consider establishing nerve centers in various geographies to coordinate the implementation of their vaccine programs. They should be prepared to adapt to different logistical requirements of the vaccines that receive approval, based on the outcomes of early clinical trials. Stakeholders should also consider the implications of multiple approved vaccines that may be launched in the same country at the same time but require different logistical considerations.
Stakeholders will need to jointly monitor vaccine rollout, as well. Vaccine developers should establish tracking programs for their products that are built on real-world evidence. Providers and developers should consider partnering to address any overlaps in monitoring—for instance, they could work to integrate product barcodes with electronic-medical-record systems.
5. Prepare now to support uptake of a vaccine
Stakeholders will need to provide key pieces of infrastructure to support the uptake of COVID-19 vaccines. For instance, insurers will need to address coverage issues for the most vulnerable populations—enabling global access to vaccines, limiting out of pocket expenses, and so on. Given the recent hesitancy to vaccinate seen in many countries around the world, healthcare and public-sector leaders may also need to mount educational campaigns that provide accurate information about new vaccines and increase public confidence. Recent polls suggest that only about 30 percent of individuals in the United States would be willing to be immunized if a COVID-19 vaccine were available in the near term.36
6. Consider endemic and postpandemic time horizons when making decisions
Innovators, manufacturers, and other key stakeholders should take a long-term view of each of the vaccine candidates in the pipeline and consider how decisions taken today could shape their relevance in the postpandemic world—especially given that one of the likely scenarios includes COVID-19 becoming endemic to some countries. In addition to ensuring that the adaptations made today will be relevant in the future, that strategy will likely make the trickle-down effects for broader preparedness become more clear. Investments made now may create opportunities for greater preparedness for future pandemics and affect the ability to onboard capacity for new vaccine technologies and platforms when they might be needed.
The timing question is becoming a bit more clear, as is the question of how much value may be created by the global launch of successful vaccines against COVID-19. Based on the established set of facts, experts agree a vaccine for COVID-19 is likely to be available somewhere between the fourth quarter of 2020 and first quarter of 2021, most likely for use in specific populations, with additional candidates coming on line by the end of 2021. In most scenarios, a vaccine will serve as a means to ensure immunity in broader populations. At a minimum, continued investment in vaccines can serve as a critical insurance policy needed to expedite the move to the next normal. Over time, lessons from the development of a COVID-19 vaccine can be built into future plans to accelerate other vaccine-development efforts.
Download the article here.