Moderna’s COVID-19 vaccine candidate protects both upper and lower airways in nonhuman primates

Moderna’s COVID-19 vaccine candidate protects both upper and lower airways in nonhuman primates

Two doses of the mRNA-1273 vaccine candidate has shown to prevent COVID-19 induced robust immune responses and rapidly control the coronavirus in the upper and lower airways of rhesus macaques exposed to SARS-CoV-2, report scientists from the National Institutes of Health.

Manufactured by Moderna, mRNA-1273 is designed to induce neutralizing antibodies directed at a portion of the coronavirus “spike” protein, which the virus uses to bind to and enter human cells.

In this study, three groups of eight rhesus macaques received two injections of 10 or 100 micrograms (µg) of mRNA-1273 or a placebo. Injections were spaced 28 days apart. Vaccinated macaques produced high levels of neutralizing antibodies against the surface spike protein of the virus.

The investigators noted that the animals receiving the 10-µg or 100-µg dose vaccine candidate produced neutralizing antibodies in the blood at levels well above those found in people who recovered from COVID-19. The vaccine-induced antibody levels exceeded with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group.

The vaccine also induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. In addition, the experimental vaccine-induced T follicular helper T-cell responses that may have contributed to the robust antibody response, the authors noted.

Four weeks after the second injection, all the macaques were exposed to SARS-CoV-2 via both the nose and the lungs. Remarkably, after two days, no replicating virus was detectable in the lungs of seven out of eight of the macaques in both vaccinated groups, while all eight placebo-injected animals continued to have the replicating virus in the lungs.

Moreover, the study pointed out that none of the eight macaques vaccinated with 100 µg of mRNA-1273 had detectable virus in their noses two days after virus exposure.

“This is the first time an experimental COVID-19 vaccine tested in nonhuman primates has been shown to produce such rapid viral control in the upper airway,” the investigators note.

A COVID-19 vaccine that reduces viral replication in the lungs would limit disease in the individual while reducing shedding in the upper airway would potentially lessen the transmission of SARS-CoV-2 and consequently reduce the spread of disease, they add.

The vaccine was co-developed by scientists at the NIAID Vaccine Research Center and at Moderna, Inc., Cambridge, Massachusetts. The findings are published online in the New England Journal of Medicine.