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Experimental Moderna vaccine protects upper and lower airways in non-human primates

Two doses of an experimental vaccine to prevent coronavirus disease 2019 (COVID-19) induced robust immune responses and rapidly controlled the coronavirus in the upper and lower airways of rhesus macaques exposed to SARS-CoV-2, report scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. SARS-CoV-2 is the virus that causes COVID-19.

The candidate vaccine, mRNA-1273, was co-developed by scientists at the NIAID Vaccine Research Centre and at Moderna Inc, Cambridge, Massachusetts. The animal study results complement recently reported interim results from an NIAID-sponsored Phase 1 clinical trial of mRNA-1273. The candidate mRNA-1273 vaccine is manufactured by Moderna.

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 neutralising antibodies directed at the surface spike protein used by SARS-CoV-2 to attach to and enter cells. Notably, say the investigators, animals receiving the 10-µg or 100-µg dose vaccine candidate produced neutralising antibodies in the blood at levels well above those found in people who recovered from COVID-19.

The experimental vaccine also induced Th1 T-cell responses but not Th2 responses. Induction of Th2 responses has been associated with a phenomenon called vaccine-associated enhancement of respiratory disease (VAERD). Vaccine-induced Th1 responses have not been associated with VAERD for other respiratory diseases. In addition, the experimental vaccine induced T follicular helper T-cell responses that may have contributed to the robust antibody response.

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 replicating virus in the lung. Moreover, 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 transmission of SARS-CoV-2 and consequently reduce the spread of disease, they add.

Abstract
Background: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates.
Methods: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens.
Results: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, 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. Vaccination induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group.
Conclusions: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.)

Authors
Kizzmekia S Corbett, Barbara Flynn, Kathryn E Foulds, Joseph R Francica, Seyhan Boyoglu-Barnum, Anne P Werner, Britta Flach, Sarah O’Connell, Kevin W Bock, Mahnaz Minai, Bianca M Nagata, Hanne Anderson, David R Martinez, Amy T Noe, Naomi Douek, Mitzi M Donaldson, Nadesh N Nji, Gabriela S Alvarado, Darin K Edwards, Dillon R Flebbe, Evan Lamb, Nicole A Doria-Rose, Bob C Lin, Mark K Louder, Sijy O’Dell, Stephen D Schmidt, Emily Phung, Lauren A Chang, Christina Yap, John-Paul M Todd, Laurent Pessaint, Alex Van Ry, Shanai Browne, Jack Greenhouse, Tammy Putman-Taylor, Amanda Strasbaugh, Tracey-Ann Campbell, Anthony Cook, Alan Dodson, Katelyn Steingrebe, Wei Shi, Yi Zhang, Olubukola M Abiona, Lingshu Wang, Amarendra Pegu, Eun Sung Yang, Kwanyee Leung, Tongqing Zhou, I-Ting Teng, Alicia Widge, Ingelise Gordon, Laura Novik, Rebecca A Gillespie, Rebecca J Loomis, Juan I Moliva, Guillaume Stewart-Jones, Sunny Himansu, Wing-Pui Kong, Martha C. Nason, Kaitlyn M Morabito, Tracy J Ruckwardt, Julie E Ledgerwood, Martin R Gaudinski, Peter D Kwong, John R Mascola, Andrea Carfi, Mark G Lewis, Ralph S Baric, Adrian McDermott, Ian N Moore, Nancy J Sullivan, Mario Roederer, Robert A Seder, Barney S Graham

 

[link url="https://www.niaid.nih.gov/news-events/experimental-covid-19-vaccine-protects-upper-and-lower-airways-nonhuman-primates"]NIH/National Institute of Allergy and Infectious Diseases material[/link]

 

[link url="https://www.nejm.org/doi/10.1056/NEJMoa2024671"]New England Journal of Medicine abstract[/link]

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