Vaccine efficacy probable against COVID-19 variants – Science Magazine

The U.S. Food and Drug Administration (FDA) emergency use authorization of three vaccines, all of which have shown greater than 85% effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1–3), has provided the public with the hope of ending the global COVID-19 pandemic. However, recent outbreaks of more transmissible variant SARS-CoV-2 strains that harbor mutations in the spike protein—the critical viral target of immune responses produced by the vaccines (13)—has invited a dour outlook on the vaccines’ continued efficacy (4). The trepidation is based on the prompt compilation of in vitro data that demonstrate as much as 10-fold reduction in neutralization antibody (NAb) activity in vaccinated samples against mutant spike protein pseudovirus (5, 6), which is thought to be an important metric of acquired immunity (7). Although reports of NAb reduction are alarming in magnitude, the proof of vaccine effectiveness can only be measured definitively by challenging vaccinated subjects with infection.

Vaccine efficacy measured by infection challenge experiments using non-human primates is often prerequisite to clinical trials, but these data are seldom articulated in lay reports. For example, in the Moderna-1273 vaccine trial (8), nonhuman primates received a 10-microgram dose [10% of the dose recommended for humans by the FDA (9)] or a 100-microgram dose (100% of the FDA dose), and researchers found a mean NAb titer of about 300 or about 3500, respectively. Despite the difference in NAb levels, both doses conferred substantial protection from infection, as measured by viral particle titers and prevention of respiratory pathology. Similar data were obtained using the Pfizer (10) and Johnson & Johnson (11) vaccines. Importantly, vaccinated samples have been tested using pseudoviral particles that express each of the SARS-CoV-2 variant spike proteins, and in each case, the samples appear to exhibit NAb titers greater than 300 in vitro (12), suggesting that vaccines will be effective against mutant strains.

These studies show that what appears to be magnitudes of difference in NAb activity may not necessarily correlate with clinical immunity. As variant strains emerge, we will need to reevaluate vaccine efficacy by testing the inhibition of viral infection in vivo rather than by quantifying the antibodies produced after in vitro exposure. Reliable proof of immunity through vaccination may only come through reinfection challenge experiments or through longitudinal studies of postvaccination subjects.