MedMaven

by Dr. C.H. Weaver M.D. updated 7/28/2020

A vaccine is needed to prevent COVID-19 and reduce the associated morbidity and mortality from transmission of the disease. Available vaccine data, initially in monkeys but now in man, shows neutralizing anti-viral antibody responses can be achieved without significant side effects. Doctors believe the antibodies are responsible for preventing re-infection because true human re-infection appears rare.

Could a vaccine actually be ready by Fall? Operation “Warp Speed” is the plan put in place by the Federal Government to achieve this goal. The plan initially focused on 125 potential vaccine candidates, was rapidly narrowed to 14 candidates in May 2020, and in June 2020, the current administration narrowed this list to 5 core candidates.(4) The published FDA guidance for vaccine effectiveness is that the vaccine prevents at least 55% of asymptomatic individuals from becoming infected which results in herd immunity assuming no changes to the current viral infectivity rate.

Vaccines in Development

Three of the five unique vaccine candidates moved forward into the next phase of clinical development this week. The Food and Drug Administration has granted Fast Track designation to 2 of Pfizer and BioNTech’s vaccine candidates against coronavirus disease 2019 (COVID-19), and data from Moderna's vaccine candidate was made available showing strong neutralizing antibody activity.

The vaccine candidates, BNT162b1 and BNT162b2, are both nucleoside-modified messenger RNA (modRNA) vaccines. Pfizer and BioNTech recently announced positive preliminary results from their early phase study evaluating BNT162b1. Initial findings from the US trial showed the vaccine candidate produced neutralizing antibody responses similar to those seen in convalescent human serology samples obtained from patients with confirmed SARS-CoV-2 infection. If regulatory approval is granted, a phase 2b/3 trial, which may include upwards of 30,000 individuals, could begin this July after an appropriate dose level is determined.

Moderna’s COVID-19 Vaccine Candidate

Moderna’s investigational coronavirus disease 2019 (COVID-19) vaccine candidate, mRNA-1273, was found to elicit neutralizing antibody activity in all study participants, according to initial trial results published in The New England Journal of Medicine. (1) For more information visit modernatx.com.

Results showed that mRNA-1273 induced rapid and strong immune response in 45 healthy adults aged 18 to 55 years. Dose dependent increases in immunogenicity were observed across all 3 dose levels and vaccine recipients demonstrated high levels of neutralizing antibody activity that exceeded those seen in convalescent sera obtained from persons with confirmed COVID-19. Further analysis is expected to provide more information on immune responses in older adults and elderly individuals.

Phase 3 Trial of COVID-19 Vaccine Candidate Begins

Moderna and the National Institutes of Allergy and Infectious Diseases have begun the pivotal phase 3 trial evaluating the vaccine candidate mRNA-1273 against COVID-19. The trial, which is the first to be implemented under Operation Warp Speed is expected to enroll around 30,000 adults and will be conducted at multiple clinical research sites across the US.

Participants will be randomized to receive 2 intramuscular injections of either mRNA-1273 or saline placebo approximately 28 days apart. The study’s primary aim will be to assess whether the vaccine is able to prevent symptomatic COVID-19. Individuals interested in participating in the trial can learn more here.

Oxford-AstraZeneca - ChAdOx1 nCoV-19 Vaccine Safe, Immunogenic

Interim results from the phase 1/2 COV00 “University of Oxford” clinical trial evaluating the vaccine candidate ChAdOx1 nCoV-19 (AZD1222) with AstraZeneca showed that vaccination led to strong immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in all evaluated participants. (6)

Initial trial results demonstrated that vaccination led to a 4-fold increase in antibodies to SARS-CoV-2 one month after vaccination and a T-cell response in all participants that peaked by day 14 and was maintained 2 months after vaccination. The vaccine a elicited neutralizing antibody responses against SARS-CoV-2 in 91% of study participants 1 month after vaccination and in 100% of participants after receiving a second dose. Phase 2/3 clinical trials are currently underway in the UK, Brazil and South Africa, and are expected to begin soon in the US.

One question that could confound vaccine development is whether the presence, or absence, of antibodies to the novel coronavirus can reliably determine immunity. A viral infection triggers a two-fold immune response that includes production of immune cells that target the virus. This includes a B-cell antibody response that can recognize a virus and lock onto it, preventing its entry into cells and a cellular T cell response that can kill both the invading virus directly and the cells it has infected.

Vaccine candidates against COVID-19 currently in the works aim to generate antibody and T cell responses, and recent findings highlight the importance of understanding the T cell response seen in human clinical trials. An optimal vaccine may need to induce both an antibody and a T cell response. There are also questions about exactly which combination of immune-system cells will result in significant protection.

Blood tests that look for antibodies are used to estimate how many people have been infected with the virus even if they never showed symptoms. But scientists still do not know how antibody levels correlate to exposure to the virus or how long they may last. Regularly measured antibodies against the virus, typically IgG, often disappear, especially in asymptomatic individuals. Evidence is increasing that some people exposed to the virus have a transient short-lived antibody response or a T cell response in spite of a minor or absent antibody response.

Some patients that have recovered from COVID-19 infection who tested negative for coronavirus antibodies go on to develop T cells in response to their COVID-19 infection. The key question for current vaccine development is whether the antibody response to the virus is robust and lasts long enough to confer a long-lasting immunity.

T cells may have a more important role in offering protection against COVID-19 than previously thought. One small French study found that six out of eight family members in close contact with relatives who had COVID-19 developed a T cell response but did not test positive for antibodies. (2) A Swedish study in 200 people also found a strong T cell response in asymptomatic individuals following coronavirus infection, regardless of whether they showed an antibody response. (3) Published in Nature this week, 23 SARS recovered patients, infected with betacoronaviruses induced multi-specific and long-lasting T cell immunity. (6)

Taken together these studies suggest that coronavirus infection rates may be much higher than what has been studied using antibody tests alone and effective COVID-19 vaccine may need to prompt T cells to work in addition to producing antibodies in order to achieve vaccine effectiveness.

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References:

  1. An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
  2. Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion
  3. Robust T cell immunity in convalescent individuals with
    asymptomatic or mild COVID-19
  4. Fact Sheet: Explaining Operation Warp Speed
  5. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
  6. [Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial](https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20%2931604-4/fulltext)
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