The Covid-19 Vaccines

Two Expected This Week and More to Follow

Both Moderna and Pfizer/BioNTech have developed vaccines based on messenger RNA (mRNA) technologies that are expected to be granted emergency use approval (EUA) in the United States this week.

An integral part of healthy aging, a Covid-19 vaccine is important although most adults will not be receiving one until this spring or early summer.

Because mRNA deteriorates easily, storage is a drawback for these vaccines. The Moderna vaccine is stable at -4 degrees F for 6 months and refrigerated for up to 30 days, whereas the Pfizer/BioNTech vaccine may be stored up to 6 months at -94 degrees F or for 15 days in specially prepared storage containers with dry ice. When thawed the Pfizer/BioNTech vaccines are stable for 5 days. Delays in transport and a common problem of new supplies sitting on hospital loading docks can complicate storage problems.

Although 300 million doses had been expected this year, the United States will be receiving approximately 50 million doses of the Moderna vaccine and 6.4 million doses of Pfizer/BioNTech’s in December, 2020, which is enough to vaccinate 28 million individuals because two vaccinations, administered 2-3 months apart, are needed.

As more of the Moderna and Pfizer vaccines arrive in 2021, we can expect the simultaneous arrival of several other promising Covid-19 vaccines.

Following the EUA of the Moderna and Pfizer/BioNTech vaccines in the United States it may be days to weeks before the vaccines are administered. In early December Britain granted EUA to Pfizer/BioNTech for their vaccination, making it available at hospitals for healthcare workers and the most vulnerable patients.

mRNA Vaccines

mRNA is a naturally occurring substance that contains an RNA version of DNA. mRNA uses this information to tell the ribosomes in cellular cytoplasm exactly which proteins to produce. mRNA has been investigated for 30 years, and while it has not been previously used in vaccines, it was approved in 2018 as therapies in ATTR amyloidosis, a condition that causes the buildup of damaging proteins.

Most mRNA therapies under development involve those that target proteins or nucleic acids and those that encode proteins. Besides its role in building proteins, mRNA turns genes off and on, a topic described further in a future article on epigenetics. mRNA therapies are currently also under development for cancer vaccines.

In the Covid-19 vaccines, a synthetic form of mRNA orders the production of the spike protein seen on the surface of SARS-Cov-2, the virus responsible for Covid-19. The presence of the spike protein elicits an immune response that causes the production of neutralizing antibodies and T cells that are ready to prevent Covid-19 from developing if SARS-Cov-2 enters the picture. Studies show that both vaccines produce more neutralizing antibodies that are produced after infection with SARS-CoV-2.

Because this is a new vaccine technology, it’s impossible to know how long immunity persists or if the vaccine confers protection against someone spreading the virus. More than 70 thousand subjects participated in phase 3 trials of the two vaccines and will continue to be monitored for two years. It’s expected that while efficacy regarding the prevention of SARS-Cov-2 infection with the Moderna and Pfizer vaccines is around 95 percent, this could change once millions of individuals are vaccinated. Adverse effects may also not be seen until a larger segment of the population is vaccinated.

Side effects at the recommended doses are reported to occur in a minority of individuals and include fever, chills, headache, and muscle pain that occur within 24-36 hours and subside within a day or two. In studies, side effects were more pronounced when higher doses than those in current use were employed. The Department of Defense has produced vaccination identification cards that will be given to individuals who are vaccinated. These vaccines have not been tested in children or in pregnant individuals.

More Covid Vaccine Candidates

There are hundreds of Covid-19 vaccine candidates under development with dozens showing exceptional promise. These vaccines use traditional technologies in which viral particles are inactivated or attenuated. This produces weak, ineffective doses of the viral vector that are still high enough for the immune system to recognize as a foreign threat and launch a robust immune response. Adenovirus strains have been successfully used as a vector in vaccines since 1980.

Oxford University and AstraZeneca’s AZd122 (COVISHIELD) is now in phase 3 trials and reported to be 70 percent effective when one dose is administered and 90 percent effective when a half dose is given in the first vaccination and a full dose in the second shot given 28 days later. A number of researchers explain that this is not unexpected when working with the adenoviruses used.

This vaccine is made from a modified non-replicating Chimpanzee adenovirus. As occurs in the mRNA vaccines, vaccination with the adenovirus vector produces the SARS-CoV-2 spike protein, which is the immune system’s primary target in Covid-19. No study participants who went on to develop Covid-19 required hospitalization or developed severe disease. India, where the vaccine is being manufactured, is conducting an accelerated review process for EUA.

Johnson & Johnson’s experimental vaccine Ensemble is in development by its Janssen division and has also received federal funding under WARP Speed. This vaccine is also vector based using a modified human adenovirus that was previously used in its European Commission approved Ebola vaccine. This vaccine also causes the production of the Coronavirus’s spike protein. The vaccine is stable for two years frozen and three months refrigerated.

Janssen began Phase 3 Trials using a single vaccination on September 23, 2020. A second Phase 3 Trial using a 2-dose regimen in a randomized, double-blind, placebo-controlled study began November 15, 2020. Thus far, participants in the United States, Belgium, Colombia, France, Germany, the Philippines, South Africa, Spain, and the UK have found the vaccine to be effective and well tolerated. Preclinical findings showed the vaccine provided complete or near complete protection against SARS-Cov-2 in the lungs and nose following a viral challenge.

Russia’s Sputnik V, a Covid-19 vaccination based on two different genetically altered adenoviruses, has been reported to be 95 percent effective after the second dose is administered based on results from a Phase 3 Trial. This vaccine, while still being investigated, has received a registration certificate from the Russian Ministry of Health and is authorized under emergency rules to be used as a vaccination in Russia.

Finding a Covid-19 Vaccination Trial

Individuals interested in participating in a clinical trial for Covid19 Vaccines can apply for screening at the CoVPN Volunteer Screening Registry at covpn.oracle.com or by calling 1-866-286-1919. The registry will notify selected individuals of opportunities in their area, including participation in some of the studies described in this article.

There are many advantages to participating in an early trial including potential early access to the vaccine. Disadvantages include not receiving the test vaccine in a randomized double-blind trial. Another disadvantage is that when a Covid-19 becomes available for your age group or medical condition, you may not be able to receive it. On the other hand at best estimate, healthy adults younger than age 62 will not have access to a Covid-19 vaccine until late spring or early summer.

Information on new vaccines will be published in Healthy Aging as it becomes available.