Vaccine news you can use

Moderna, Inc. today announced outstanding early data for its Covid-19 vaccine candidate, in a trial led by the National Institute of Allergy and Infectious Diseases (most Americans will recognize NIAID as Dr. Anthony Fauci’s agency), which is part of the National Institutes of Health. Key points from the press release follow, with some plain English translation.

Dose dependent increases in immunogenicity were seen across the three dose levels, and between prime and boost within the 25 µg and 100 µg dose levels. All participants ages 18-55 (n=15 per cohort) across all three dose levels seroconverted by day 15 after a single dose. At day 43, two weeks following the second dose, at the 25 µg dose level (n=15), levels of binding antibodies were at the levels seen in convalescent sera (blood samples from people who have recovered from COVID-19) tested in the same assay. At day 43, at the 100 µg dose level (n=10), levels of binding antibodies significantly exceeded the levels seen in convalescent sera. Samples are not yet available for remaining participants.

At this time, neutralizing antibody data are available only for the first four participants in each of the 25 µg and 100 µg dose level cohorts. Consistent with the binding antibody data, mRNA-1273 vaccination elicited neutralizing antibodies in all eight of these participants, as measured by plaque reduction neutralization (PRNT) assays against live SARS-CoV-2. The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera.

Translation: The trial is looking for the best dose, and tested three dose levels on 15 patients each, for a total of 45 patients, two administrations of vaccine for each. Every patient developed some antibodies within two weeks of the first dose. Eight patients progressed to 43 days, which is two weeks after the second dose, and all 8 developed antibodies at or higher than levels seen in patients who have recovered from Covid-19.

The vaccine candidate was generally safe and well-tolerated, and a Phase 3 trial (the trial designed to prove safety and effectiveness to statistical significance, which is needed for regulatory approval) will begin in July.

For those of you for whom hope is a strategy, which is most of us, this news is very good.

The prospects for a vaccine against Covid-19 are very good, hedging about the durability of immunity notwithstanding. There are more than 100 other programs working on Covid-19 vaccines around the world, and tremendous pressure, including geopolitical competition, to get to the finish line first.

Following, a fair use excerpt from a Wells Fargo analytical report on vaccine programs (sadly, no link):

Summary. This is the inaugural issue of our Covid-19 Vaccine Tracking Report. In this report, we are tracking a select set of vaccine candidates targeting the novel coronavirus designated SARS-CoV-2. These candidates must meet three criteria: (a) currently in human
clinical trials, or with imminent starts, (b) sufficient capitalization to
carry through multiple R&D stages, and (c) partnerships or
manufacturing plans to credibly release substantial quantities of
vaccine within the next year.

Current Situation. Well over a hundred Covid-19 vaccine candidates
are in various stages of research and development. These vaccine
candidates target the SARS-CoV-2 virus, typically one or more aspects
of that virus’s spike (S) protein. Virtually every vaccine type that has
ever succeeded with some other pathogen (e.g., inactivated, subunit,
vectored) or is viewed as promising new technology (e.g., DNA, mRNA) is being explored. Our three criteria lead us to track ten vaccine candidates being developed by BioNTech, CanSino, Inovio, Johnson & Johnson, Moderna, Novavax, Sanofi, Sinopharm, Sinovac, and the University of Oxford (alphabetically by sponsor)….

Timing: We anticipate that positive data at end of phase 2 trials could
be sufficient to trigger EUA [Emergency Use Authorization] status with national regulators. Based on public statements to date, this could be as soon as late 2020 for several of the candidates. At present, JNJ and SNY project later trial starts and thus later EUA decision points. Presumably, those two companies are assessing how to compress their own development timelines. Once products are distributed under EUA status, some of the highest risk populations can be offered some degree of protection. Meanwhile, data collection will continue, even as distribution broadens, to build the evidence base that would warrant full reviews and approvals from FDA, EMA, and their counterparts
around the world.

For whom: We expect initial supplies of Covid-19 vaccines to be focused on people at highest risk of infection or essential to community function. Some of these will be occupational groups (e.g., healthcare workers, first responders, grocery-store workers, schoolteachers). Others will be social groups (e.g., nursing-home residents, seniors, communities with high attack rates). Starting points for prioritizing vaccine distribution will be similar to those used in previous vaccine shortages (e.g., influenza vaccine in 2004 and 2009)….

Assessment of Production Capacity. Ideally, to assess leading manufacturers’ plans for Covid-19 vaccine production capacity, each company would describe a common set of production goals and corresponding dates. For example, doses to be produced through December 2020, as well as goals for doses per month to be released in June 2021 and in December 2021. In reality, the companies’ public statements provide varying levels of detail, tempered by uncertainties inherent to technology transfer, industrial scale-up, facility repurposing or construction, dosing requirements not yet settled, regulatory approvals, and related factors. A major source of uncertainty will be resolved for each candidate once the human dose is set for the phase-3 trials of vaccine efficacy. The quantity of protein per dose bears directly on how many doses can be produced from any given manufacturing asset (e.g., fermenter).

Bold emphasis added.

The very last point provides some important context for the Moderna trial discussed at the top of the post. Why not just go for the highest safe dose to get the most robust antibody levels? Because that will slow down production and delay vaccination for millions of people. The dose determination needs to be optimized, not for profits — although we certainly expect some ignorant sniping in that direction once the popular press starts focusing on dosing decisions — but to maximize the number of people who can get the vaccine, even if some of those people will not develop antibody levels that confer perfect immunity. Whether there is a magical dose level for any safe and effective vaccine that reliably confers immunity and allows for grillions of doses very quickly remains to be seen.

Stay tuned.