The mRNA vaccine co-developed by Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) protected both the upper and lower airways of non-human primates against SARS-CoV-2 infection.
Rhesus macaques receiving low or high doses of mRNA-1273 vaccine (10 or 100 μg, two injections 4 weeks apart) were then challenged with the virus via both the nose and the lungs a month after the second injection. Seven of eight vaccinated monkeys in both dosing groups had no detectable virus in the lungs two days afterwards, whereas viral RNA was found in lungs of all eight monkeys receiving placebo, according to Barney Graham, MD, PhD, of NIAID, and colleagues.
And all monkeys receiving the higher dose of vaccine had no detectable virus in their noses two days after the nasal challenge, compared with three of eight in the low-dose group and two of eight receiving placebo, Graham’s group reported in the New England Journal of Medicine.
“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 transmission of SARS-CoV-2 and consequently reduce the spread of disease,” the NIAID said in a statement.
Graham and colleagues compared these results to earlier findings with the so-called Oxford vaccine — an adenovirus-based product — and with a different DNA-based vaccine, both of which also provided protection against lower airway replication in macaque challenge studies.
“However, these studies provided no evidence of a reduction of a viral replication in nasal tissue, raising questions as to whether these vaccines could affect virus transmission,” they wrote.
Previously, interim phase I/IIa data showed the Moderna vaccine was well-tolerated and produced an immune response in healthy volunteers. Moderna announced Monday that it had begun dosing in a phase III trial, expected to comprise 30,000 individuals with half receiving the vaccine and half receiving placebo.
“We are participating in the launching of a truly historic event in the history of vaccinology,” said NIAID Director Anthony Fauci, MD, at an NIAID press briefing on Monday. “Right now, we are concentrating on sites in the U.S. [with] enough transmission activity going on that we will get endpoints from that,” he said.
Fauci said vaccine efficacy of at least 60% is a major goal, because that will provide enough statistical power to say whether or not the vaccine is effective. Currently, given the rate of infection, Fauci estimated efficacy data for phase III will likely not be available until the end of the year.
With trials ongoing, Graham and colleagues provided a rationale for using non-human primates to help assess immunogenicity, saying they are similar to humans in “innate immune responses and B-cell and T-cell repertoires and allow for the use of clinically relevant vaccine dose.” They added recent studies found SARS-CoV-2 targets similar replication sites in non-human primates as in humans, as well.
The Moderna vaccine prompted a dose-dependent antibody response in macaques, with neutralizing activity at 4 weeks after the first vaccination 5 times higher among animals who received the higher dose versus the lower dose of vaccine. S-specific IgG and neutralizing geometric mean titers at 4 weeks after the second higher dose of the vaccine were 5 and 15 times as high, respectively, than seen in convalescent-phase serum collected from human COVID-19 survivors.
Th1 T-cell responses were also seen in the animals, but Th2 responses were low to undetectable in both vaccinated groups — a desired outcome, the NIAID noted in a statement, since Th2 responses are associated with vaccine-associated enhancement of respiratory disease.
One obvious limitation to the study is how well the macaque model mirrors COVID-19 development. Graham and colleagues acknowledged that the amount of virus necessary to trigger human infection is unknown; however, virus concentrations in the upper airways of COVID-19 patients were similar to those found in macaques’ nasal passages a day after challenge.
This study was supported by the Intramural Research Program of the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID), NIH, and the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, Department of Health and Human Services.
One co-author disclosed a research fellowship from the Undergraduate Scholarship Program, Office of Intramural Training and Education, Office of the Director, NIH.
One co-author was funded by grants from the NIAID and a Burroughs Wellcome Fund Postdoctoral Enrichment Program Award.