With the number of COVID-19 cases in Malta on the rise, I thought it would be useful to you, as Business Leaders, if I can provide you with an in-depth review of the COVID-19-vaccine situation. I have looked at publicly available information on the potential time to develop a COVID-19 vaccine as well as potential barriers, taking also notice of what is being said both by world experts in epidemiology and public health, as well as important participants in the vaccine ecosystem i.e. developers, funders etc..

The good news……

Vaccine developers 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 the 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. (For example, it took four years to develop the mumps vaccine, which was previously the fastest developed novel vaccine. )

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. However, 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 finalising guidelines for COVID-19 vaccines. For example, recent guidance from the US Food and Drug Administration (FDA), 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.

What is emerging as being critical is the fact that 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 & monitoring; prepare now to support uptake of a vaccine; and consider endemic and postpandemic time horizons when making decisions.

It is at the end of the day, a question of timing, with the 1 million dollar question on everyone’s mind being “By when will we have a vaccine?” 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.” 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. However here I present a more detailed 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.

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. 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. 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.”

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 neutralising antibodies in more than 90% of people who were tested 14 days after receiving two injections two weeks apart, with no severe adverse events reported.

Then, the 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%of participants who received two doses over 28 days developed neutralizing antibodies. I

In early July, Pfizer and BioNTech published preliminary results from a Phase I clinical trial of their candidate, indicating positive results.

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 neutralising antibody titers using both a live virus and a pseudovirus.

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% of participants one month after injection.

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% of participants and a T-cell response within 14 days of receiving the vaccine.

Further data on those and other vaccine candidates are needed, but initial results point to the idea that candidates are developing neutralising antibodies to some degree.

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. 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.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. 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

Besides the ones mentioned above, there are more than 250 announced COVID-19 vaccine candidates globally, with more than 50 planned entries into human clinical trials in 2020. 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). To get a better sense of the likely number of successful candidates, if one where to base himself on the historical probabilities of success in vaccine development and the existing pool of announced candidates, one can conclude 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.

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. Governments, nongovernmental organisations, and private companies are making similar monetary commitments, with a substantial portion of the funds being directed toward individual vaccine candidates.

The not so good news….

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—four in particular: validating unproven platform technologies, demonstrating protection against COVID-19; targeting the appropriate vaccine design and regulatory considerations

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. 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 immunised 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 immunised. 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.

Regulatory considerations. 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.

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.