From Brief19: Message in a bottle. Moderna’s mRNA vaccine ca | Figure 1

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From Brief19: Message in a bottle. Moderna’s mRNA vaccine candidate makes a splash

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May 19, 2020

In the past few years, the prospect of a producing vaccines that use messenger RNA instead of proteins derived from infectious pathogens including viruses and bacteria has captivated the biotechnology industry. While potential vaccines for many diseases have been synthesized, none have been approved for use anywhere in the world.

Yesterday, Moderna, a company in Massachusetts, announced favorable results from a phase 1 trial testing their first vaccine candidate against SARS-CoV-2. Phase 1 trials are designed to establish doses and safety profiles for drugs and vaccines in development. Generally, phase 1 trials are small and enroll 20 or more test subjects. In addition to reporting on the safety of the vaccine—which so far appears to have caused only minimal side effects—the company announced that the vaccine, known as mRNA-1273, elicited an immune responses in the first eight volunteers who received the vaccine for whom data is currently available. This candidate vaccine is composed of genetic material (mRNA) that codes for a spike protein which extrudes from the surface of SARS-CoV-2 particles. While the theory is well-grounded, reality is what matters. It is therefore encouraging that blood later drawn from test subjects in this phase 1 study exhibited antibody levels that were similar or higher than the levels that have been detected in patients known to have recovered from SARS-CoV-2 infection. The company reports that all participants in the study "seroconverted" with respect to neutralizing antibodies, regardless of the dose given. This suggests that the subjects' immune systems recognized the vaccine appropriately ("immunogenicity") though it does not necessarily mean that these responses rendered the patients immune. But there appears to be good news on that front as well. The first eight patients were also found to have mounted "neutralizing" antibody responses 43 days after the vaccines were given. The blood from these patients were taken to labs and placed on plaques of viral particles. The plaques were observed to have been reduced in size, suggesting that the viral particles were being effectively killed. The levels of neutralizing antibodies were either similar or greater than those observed in blood from recovered covid-19 patients ("convalescent sera").

Based upon these findings, the FDA has permitted a phase 2 trial to begin on an expedited basis, which will further assess the safety of the vaccine using the dose that appears to be most promising. Hundreds of patients are to be enrolled.

Generally, potential drugs and vaccines that carry serious but rare side effects are unlikely to be detected in phase 1 trials. The results of phase 2 data (as well as a phase 3 trial which would include thousands of patients and is already being planned for rollout as soon as July) will be watched closely for this reason. If the vaccine works but causes unacceptable rates of serious side effects during phase 2 or phase 3 trials, it would be back to square one. Nevertheless, the stock market rewarded this news in trading yesterday.

Shared with permission from Brief19, a daily review of #covid-19 research and policy.

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