75 COVID Vaccine Candidates – Winner Is?

Over 75 vaccine candidates to address COVID-19, also known as SARS-CoV-2, are in the pipeline according to the World Health Organization (WHO) as of April 20, 2020.

The majority of these, however, remain far from clinical trials. Wells Fargo Securities’ Health Care Team has begun to track the progress of the 10 most advanced vaccine candidates. Six vaccine candidates are expected to have phase 2 results available by the end of 2020, which would allow them to be granted Emergency Use Authorization (EUA) before the end of the year. Wells Fargo points out that even with positive clinical data, production of enough doses of vaccine for widespread application is still unclear and projections depend on how much vaccine protein is required per dose.

The Centrality of COVID Vaccines to a Return to Normal

Despite relaxation of lockdown or shelter-in-place orders in numerous jurisdictions the threat of acquiring COVID-19, the disease caused by the novel coronavirus, also known as SARS-CoV-2, is still present. The disease has the potential to cause severe illness even in healthy individuals. Additionally, the high fatality rate among at-risk populations, such as the immune compromised, elderly, and those with cardiovascular or respiratory co-morbidities, makes a return to normalcy frightening for many.

To be confident that one will not contract the disease, or spread it to a loved one, the population needs to achieve herd immunity, which is when enough people have immunity that outbreaks are minimized, and infection cannot spread uncontrollably. The best way to achieve herd immunity is through development and widespread adoption of a vaccination program. Vaccines have helped to eliminate, or virtually eliminate, countless disease that once caused significant numbers of fatalities, such as smallpox, measles, polio, and tetanus.

The problem with the current pandemic is that nearly the entire global population is naïve to SARS-CoV-2, and the virus is not similar enough to other viruses that already have vaccines developed. A naïve population means that the virus can spread easily through exposure as no one had immunity to it from prior exposure.

The Largest Current Vaccine Trial

Thanks to recent developments in vaccine technology such as DNA and mRNA-based vaccines, several vaccines have been developed within hours or days of sequencing the virus responsible for COVID-19. However, despite rapid design of vaccines using these methods, the resulting product must still undergo rigorous testing. Even with relaxation of regulations, trials must still be carried out carefully, with sufficient numbers, and over a sufficient length of time to be certain of their safety and efficacy.

The largest trial currently underway is for the mRNA-based vaccine from BioNTech, a German biotech that specializes in individualized cancer therapeutics. The trial is being conducted in Maryland, New York, and Ohio, with 7,600 patients to be enrolled. Phase 2 data for the trial is expected by May 2021. BioNTech is partnered with Pfizer, Inc. and is expected to be capable of scaling up production into the hundreds of millions by the end of 2021.

One of the most advanced candidates is an mRNA-based vaccine from Moderna, Inc., a Massachusetts-based biotechnology company. Phase 2 data from Moderna’s candidate is expected in November 2020, and Phase 1 results are expected by the end of May. The FDA granted fast-track status to the Moderna candidate on May 12. Wells Fargo expects that the company, through its partnership with Lonza Ltd can produce up to 1 billion doses per year, assuming dosing at the lowest concentration being tested.

Another issue that Wells Fargo has pointed out is that all trials are currently being conducted with adults, meaning that current vaccines if and when approved may not include an indication for children, leaving the young unimmunized and potential carriers of the virus.

JAMA’s Post Infection Immunity Study

An important factor that must be considered is the durability of immunity provided either through prior infection by the virus, or vaccination. A publication in the Journal of the American Medical Association (JAMA) in May 2020 by epidemiologists at the Centers for Disease Control and Prevention (CDC) titled, “COVID-19 and Post infection Immunity: Limited Evidence, Many Remaining Questions” suggests that continued antibody presence is unclear.

The authors point out that no reinfections have yet been confirmed, but reinfection has occurred in other common human coronaviruses, which cause minor respiratory illness. Antibodies to SARS-CoV-1 and MERS-CoV, the viruses that caused epidemics of SARS in 2004 and MERS in 2012, were found up to 2-3 years after infection.

However, because the viruses have not been observed since the initial epidemics, it is not clear if antibodies were protective against reinfection. The authors conclude that current evidence suggests that at least temporary immunity is conferred through infection. Presumably vaccination would also confer immunity. If immunity is found to be temporary, a regular vaccination schedule will be necessary, putting additional stress on the production of new vaccine. Distribution of the vaccine will already be prioritized to particular occupational and health-status groups, potentially leaving “non-essential” or not at-risk individuals without a vaccine for months or years after one is finally approved.

Operation Warp Speed

On May 15, 2020, President Trump announced “Operation Warp Speed” to develop and deliver a vaccine by the end of 2020. Former head of vaccines at GlaxoSmithKline plc, Moncef Slaoui, has been selected to lead the mission. He was quoted as saying that he is “Confident that we will be able to deliver a few hundred million doses of vaccine by the end of 2020,” after having seen preliminary data for an undisclosed vaccine candidate.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease (NIAID), said during a hearing before the U.S. Senate HELP Committee on Tuesday, “There’s no guarantee that the vaccine is actually going to effective…. I still feel cautiously optimistic that we will have a candidate that will give some degree of efficacy.”

While there is no guarantee that the U.S. plan to have a vaccine approved and in production by the end of the year there are several candidates that, if successful, will be available during 2021. It will likely take several months more for the majority of the population to receive the vaccine as world-wide allocation and distribution is sure to be another bureaucratic stumbling block that has yet to be determined.

With consideration of function and the capabilities of the manufacturer and partners, Wells Fargo expects that production of the Johnson & Johnson, Moderna, and Novavax vaccine candidates could well be the greatest.