The Rush to a Vaccine

TLDR: Impact of disease unequaled; Vaccine development accelerated 10x; Safety of the vaccine development process preserved

From the determination of a genetic sequence to the first human clinical trials of a vaccine typically takes the better part of a decade. In the case of SARS-CoV-2, this has been accomplished in 6 months!

Patients ask whether this breakneck pace is safe.

So far, it appears to be.

Traditionally, vaccine development occurs in discrete phases that occur sequentially. In the case of the novel Coronavirus, various research activities are happening simultaneously. We know that some of these efforts will produce no useful information. While not the most cost-effective approach, the economic destruction caused by the virus justifies the expenditure to tame it.

As of mid-July, SARS-CoV-2 had infected more than 12 million people, claimed more than a half-million lives, and cratered economies around the world. 

The first of three reports from a Phase 1 trial of an mRNA vaccine developed by Moderna was published on 07/14/20. In this paper, short-term results for subjects age 18-55 were reported. We will likely see a second publication, reporting on subjects age 55 and older, and a third to describe the durability of the immune response.

The paper describes a small study with only 45 participants. But all of these subjects developed meaningful antibody levels in response to vaccination. This is excellent early news in the war on COVID. For Moderna, the next step is a large Phase 3 trial which should begin enrolling subjects in late July 2020.

On Monday 07/20/20, Phase 1 trial results were published for two additional vaccines that use a different technology (an “adenovirus vector”) to increase the effectiveness of the vaccine. This is a very new technology, having been developed for use in attempts to find an Ebola virus vaccine.

The first, a study from Wuhan, China, using a vaccine developed by CanSino Biologics, enrolled 508 adults not previously exposed to SARS-CoV-2. Two doses of vaccine were compared with placebo in subjects age 18-83 years. Many subjects had fatigue, headache, fever, or injection site pain, but there were no serious adverse events. More than 96% of subjects developed antibodies, and more than 90% had T-cell responses. T-cells are the “other half” of the immune system, working in the longer term. Both men and women responded to the vaccine. While antibody levels were lower in older subjects, the T-cell response was similar over all ages.

Interestingly, men developed post-vaccination fever less frequently than did women. Among the mysteries of COVID-19 is that while the number of COVID-19 cases appears to be comparable between men and women, men develop more severe disease and are twice as likely to die as a result of infection. It is not yet clear whether this difference is related explicitly to gender or other variables. For example, smoking, alcohol consumption, and heart disease are all more prevalent in men than in women.

The second study was even larger, with 1,077 participants and was conducted in the United Kingdom by The Jenner Institute at Oxford University with support from AstraZeneca. Subjects were given a single dose of a chimpanzee adenovirus-vectored vaccine, or a comparator meningococcal vaccine. Fatigue, headache, and other local and systemic minor adverse reactions were common, but there were again no serious adverse events. T-cell responses were demonstrated in all subjects, and more than 90% of subjects developed neutralising antibodies. These responses were sustained to at least 56 days post-vaccination (the duration of the trial).

There are currently four vaccines (developed by Moderna, AstraZeneca/Oxford University, Johnson & Johnson, and Pfizer/BioNTechSE) with planned Phase 3 trials to start this summer. Another dozen or so vaccines are to enter Phase 1 or 2 studies this summer. Overall, more than 120 candidate SARS-CoV-2 vaccines are in development.

Phase 3 trials will involve much larger subject populations (30,000 in the case of the planned Moderna study) and should lead to definitive data regarding the safety and efficacy of vaccination for SARS-CoV-2.

The safety data from each of these trials is very reassuring. This is critical as studies proceed because the public acceptance of a vaccine will depend on well-run trials.

Many questions remain. Will one dose be sufficient, or will a booster be needed? Will different vaccines be more effective for various age groups? How long will the protection last? Will antibody levels or T-cell responses determine effectiveness in preventing disease?

We are cautiously optimistic that a safe and effective vaccine for SARS-CoV-2 will be available in the fall of 2020.

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