Unlike in mice and nonhuman primates, low-level virus replication in mRNA-1273Cvaccinated hamsters coincided with an anamnestic response. of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock-vaccinated hamsters. Our results support the use of mRNA-1273 in a 2-dose schedule and provide insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2. = 15) were vaccinated with 25 g, 5 g, and 1 g of mRNA-1273 via the intramuscular (i.m.) route in a prime (week 0)Cboost (week 3) regimen (Figure 1A). One group of hamsters (= 15) received a prime-only dose of 25 g at week 0, and another group (= 15) were mock vaccinated as the studys control. The humoral responses to vaccination were measured by ELISA specific for the SARS-CoV-2 S protein (Figure Ro 48-8071 1B) and its receptor-binding domain (RBD) (Figure 1C). Three weeks after the prime dose, higher S-specific IgG titers were detected in hamsters vaccinated with 25 g and 5 g doses compared with the 1 g dose (Figure 1B). S-specific IgG titers were significantly augmented in all groups following the booster, but continued to be significantly higher in the 25 g and 5 g dose groups compared with the 1 g dose group. RBD-specific IgG titers were comparable among hamsters in the prime-boost regimen groups after receipt of their first dose (Figure 1C). After a boost dose, RBD titers had increased significantly (0.0001) and remained comparable among the prime-boost groups. RBD titers in the prime-boost vaccine groups were also significantly higher after the second dose in comparison with the 25 g prime-only group (0.0001), while titers remained unchanged for the 25 g prime-only group between weeks 3 and 6 after vaccination. The ability of serum to neutralize live SARS-CoV-2 reporter virus was also determined (Figure 1D and Supplemental Methods; supplemental material available online with this article; https://doi.org/10.1172/JCI148036DS1). Most vaccinated hamsters produced neutralizing titers after the prime dose. As with RBD-binding titers, neutralizing Ro 48-8071 titers significantly increased in all groups that received a booster dose, and the levels remained comparable among these hamster groups, but higher versus the prime-only vaccine group. The Ro 48-8071 magnitude of neutralizing antibody titers in all booster-vaccinated groups was higher than in convalescent COVID-19 patients, while titers in the prime-only group were comparable to those seen in these subjects. Neutralizing titers significantly correlated with S-specific IgG titers (Supplemental Figure 1A) and RBD-specific titers (Supplemental Figure 1B), albeit the correlation was greater with RBD-specific IgG titers at both week 3 and week 6 after vaccination. Open in a separate window Figure 1 Serum antibody responses in vaccinated hamsters.(A) Study design. Hamsters were prime-vaccinated via the i.m. route at week 0 and boosted at week 3, with 25 g (15), 5 g (15), and 1 g (15) of mRNA-1273. A group of hamsters (15) received a prime dose only of 25 g mRNA-1273, and a mock group received PBS (15) at week 0. At week 6, animals were intranasally challenged with 105 PFU of SARS-CoV-2. On days 2, 4, and 14 after infection, hamsters (5 per group) were euthanized for tissue collection. PRNT, plaque reduction neutralization test (BCD) Total serum SARS-CoV-2 SCspecific (B) and RBD-specific (C) IgG titers in serum and neutralizing titers (D) in hamster groups prior to SARS-CoV-2 infection measured by ELISA and plaque reduction assays, respectively. Neutralizing titers were compared with a panel of human convalescent serum samples (Conv.). Bars denote group means SE. Significance was measured by ANOVA with Tukeys or ?idks correction for multiple comparisons between vaccine groups or between time points, respectively (*0.05, **0.01, ***0.001, ****0.0001). Prime-boost vaccination effectively protects against SARS-CoV-2 replication in the lungs. Six weeks after prime vaccination (3 weeks after the boost vaccination), all treatment-group hamsters were challenged intranasally with 105 plaque-forming units (PFU) of SARS-CoV-2. Hamsters were monitored daily for changes in Rabbit Polyclonal to ERCC5 body weight. At 2 and 4 days postinfection (dpi), 5 animals from each group were serially euthanized, and the viral load in the right lung and nasal turbinates was determined. The remaining hamsters were observed until the studys endpoint at day 14. Mock-vaccinated hamsters lost an average maximum body weight of 12% by day 6 (Figure 2A and Supplemental Figure 2, A and B). The prime-boost regimen.