1. Nonhuman primate vaccination with messenger RNA (mRNA)-1273 induced rapid neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
2. The mRNA-1273 vaccine conferred upper and lower airway protection with no pathologic changes in the lungs.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the 2020 Covid-19 global pandemic. To combat the ongoing pandemic, vaccine development is essential. Current vaccine strategies focus on nucleic acid vaccines, whole-inactivated SARS-CoV-2 vaccines, and subunit protein vaccines. The novel use of messenger RNA enables quick modification of the encoded immunogen and faster manufacturing accelerating vaccine development. As such, this study evaluated neutralizing antibody response of the mRNA-1273 vaccine by preventing upper- and lower-airway infection in nonhuman primates. The study determined that the mRNA-1273 vaccine had a rapidly neutralizing response against SARS-CoV-2 without altering the lung architecture. This randomized trial was limited by the follow-up period after the initial vaccine administration. The study analyzed immunity response and maintenance seven days after vaccine administration. As symptom presentation for SARS-CoV-2 can take up to 14 days, the analysis should have encompassed a 14-day follow-up period.
In-Depth [randomized controlled trial]: This randomized control trial studied 24 female and male Indian-origin rhesus macaques ranging from 3 to 6 years of age. The nonhuman primates were stratified into groups of three based on sex, age, and weight. Within each stratified group each of the animals were arbitrarily assigned to one of the following treatments: 10 μg of mRNA-1273, 100 μg of mRNA-1273, or phosphate-buffered saline as the control. The vaccines were administered at week 0 and week 4, after which, the animals were challenged with 7.6×105 plaque-forming units of SARS-CoV-2 at week 8. The analysis included viral RNA that was quantified through polymerase chain reaction, serum antibody measurements, and histopathology of lung specimens. The neutralizing activity increased in a dose-dependent manner. After the second vaccination, the reciprocal 50% inhibitory dilution (ID50) geometric mean titer (GMT) for the 10 μg vaccine was 103, and the ID50 GMT for the 100 μg vaccine was 1,862. Furthermore, the SARS-CoV-2 spike protein-specific IgG binding and neutralization were 5 and 15 times higher, respectively, for the 100 μg vaccine compared to the 10 μg vaccine. Protection of the upper respiratory tract from the virus was analyzed through nasal secretions. Animals vaccinated with either the 10 μg vaccine (P=0.003) or the 100 μg vaccine (P=0.03) had a significantly lower total RNA levels compared to the control group. Protection of the lower respiratory tract form the virus was analyzed through bronchoalveolar-lavage fluid. The total RNA levels were significantly lower in both dose groups compared to the control group (P<0.001). Finally, the pathology of SARS-CoV-2 in lung tissue specimens was analyzed. The specimens from the control group presented with moderate-to-severe inflammation involving the small airways and adjacent alveolar interstitia. Additionally, alveolar capillary septa were thickened and type II pneumocyte hyperplasia was observed. The pneumocytes were positive for SARS-CoV-2 viral RNA and antigen. The specimens from the 10 μg vaccine group presented with mild inflammation and no detection of viral RNA. Lung histology from the 10 μg dose group showed no inflammation and no detection of viral RNA or antigen in the pneumocytes. Taken together, the mRNA-1273 vaccine neutralized SARS-CoV-2 activity, while providing protection to the upper- and lower- airways of nonhuman primates.
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