The coronavirus disease 2019 (COVID-19) pandemic continues to spread across the globe. Vaccination efforts against its causative agent – the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – have commenced in many parts of the world.
One of the vaccines currently being rolled out is the mRNA-1273 (or Moderna) COVID-19 vaccine. US-based researchers have demonstrated that the prime or prime-boost vaccination of mRNA-1273 vaccine in hamsters induced robust neutralizing antibodies, ameliorated weight loss, and suppressed SARS-CoV-2 replication in the airways.
The team – from the University of Texas Medical Branch, Princeton University, Icahn School of Medicine at Mount Sinai, and Moderna Inc. – have released their findings on the bioRxiv* server.
Moderna COVID-19 vaccine
The Moderna COVID-19 vaccine, also called mRNA-1273, is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of SARS-CoV-2. In short, it allows the host to develop neutralizing antibodies against the spike protein antigen of the virus, which effectively prevents SARS-CoV-2 virions from latching onto and infecting cells if the host becomes exposed.
Manufactured by ModernaTX, Inc., the vaccine is for preventing COVID-19 in people who are more than 18 years old.
The study demonstrated that administering a prime-boost of mRNA-1273 generated a strong neutralizing antibody response and prevented the replication of the virus in the airways.
Though the vaccine has been used in human trials, these cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that can cause more severe SARS-CoV-2 disease, akin to hospitalized patients. This makes hamsters relevant for vaccine evaluation.
To arrive at the study findings, the researchers tested the effectiveness of the Moderna vaccine with prime only and three-dose levels of prime-boost regimens using the stringent golden Syrian hamster model. They performed a series of tests and analyses to characterized vaccine-mediated immunity before and after the challenge.
The team has found that vaccinating hamsters with the mRNA-1273 vaccine triggered strong neutralizing antibody responses, suppressed the influx of inflammatory innate immune cells, and the decreases in white blood cells in the lungs.
Three groups of hamsters were vaccinated with 25 µg, 5 µg, and 1 µg of mRNA-1273 in a prime-boost regimen. One group received the prime only dose of 25 µg at week 0 and another group receives placebo vaccines. The team observed and measured the humoral responses to vaccination by enzyme-linked immunosorbent assay (ELISA) specific for the protein in SARS-CoV-2 and its receptor-binding domain (RBD).
Three weeks after giving the prime dose, higher S-specific immunoglobulin G (IgG) titers were seen in the hamsters who received the 25 µg and 5 µg doses compared to the 1 µg dose. Further, S-specific IgG titers were markedly amplified in all groups following the booster. However, the 25 µg and 5 µg dose groups had higher S-specific IgG titers.
Overall, the study showed that two doses of mRNA-1273 vaccine reduced viral load in the upper and lower airways of hamsters, and protected against weight loss. A prime-only vaccination only provided partial protection. Meanwhile, two doses of mRNA-1273 are necessary to stimulate neutralizing titers akin to the higher titers seen in convalescent COVID-19 patients.
The most effective dosage was the 25 µg, which provided better protection against lung injury and weight loss.
mRNA-1273 demonstrated protection is predominately achieved through the induction of antibodies, and cellular responses may act to support complete clearance of the virus. Importantly, the safety of mRNA-1273 was indicated by the absence of aberrant cellular pathways in VI hamsters after challenge,” the researchers concluded in the study.
The team also urged further studies to explore how immunity induced by other vaccines is regulated following infection to provide the foundation for a better vaccination campaign.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.