200 COVID-19 Vaccine Candidates in Pipeline
Currently, there are over 200 vaccine candidates in various stages of development. However, fewer than a dozen are being tested and produced by companies that have sufficient funding, and partnerships to complete clinical trials and produce quantities in the millions to billions of doses, according to Wells Fargo Securities’ Health Care Team.
The promise of a vaccine by the end of 2020, or early 2021, comes with several caveats that will impact the availability of the vaccine. A candidate may complete phase 2 trials with sufficient evidence to warrant Emergency Use Authorization (EUA), Conditional Marketing Authorisation (CMA), or Emergency Use Listing (EUL) from regulatory bodies in the U.S., European Union, and World Health Organization, respectively.
Unfortunately, these compassionate use statuses will not allow the vaccine to be used for the general population. Additional testing may be necessary for full approval. Specific essential occupations or social groups may be selected for early vaccination while the general population waits.
Several partnerships have promised millions of doses to the U.S., UK, EU, and other regions. For example, a partnership between Oxford and AstraZeneca is testing and producing a chimp adenovirus-vector vaccine with commitments of 30 million doses to the UK, 300 million doses to the U.S., 400 million to the EU, and over 1 billion to other regions.
As far as clinical trial progress is concerned, the earliest phase 2 trial completion is expected by November 2020 for Moderna’s mRNA candidate. EUA may be possible for this and a few other candidates in November or December, but this does not mean widespread delivery and administration until the product is approved more broadly and licensed. The earliest licensure is expected to be in March 2021 after phase 3 data is available for Moderna and BioNTech’s mRNA candidates, and Sinovac Biotech’s inactivated virus vaccine.
Another concern is efficacy, or how well the vaccine protects against infection. Current reports based on preliminary data are promising. Data show that neutralizing antibodies are found in patients receiving vaccines from Moderna, Sinopharm, Sinovac, and University of Oxford/AstraZeneca. However, neutralizing antibodies do not guarantee efficacy. Several vaccine types (mRNA, DNA, adenovirus, inactivated virus, and recombinant protein) are currently being developed and trialed, hopefully increasing the odds of a successful candidate.
Recent controversies over unintended side effects of vaccines should, at the very least, suggest that due diligence is critical.
Widespread use of Dengvaxia, a Dengue Fever vaccine, in the Philippines, resulted in the death of over 600 people, mostly children, between 2015 and 2019. After investigation, it was determined that dengue-naïve children who received the vaccine were more likely to acquire a severe form of the disease after later exposure due to antibody-dependent enhancement (ADE).
Similar issues were observed with the respiratory syncytial virus (RSV) vaccine developed in the 1960s. Some early studies have proposed that ADE may be relevant in SARS-CoV-2 infection, leading to more severe disease in individuals with antibodies against other coronaviruses, however more studies are needed to make conclusions. With the recent concerns highlighted by Dengvaxia, it is likely that ADE is a concern of virologists and vaccinologists working on the current COVID-19 vaccine candidates.