Fig. 6: mRNA-VLP vaccine immunogenicity and protection of hamsters from SARS-CoV-2 virus challenge.

A Four groups of Syrian golden hamster (n = 16/group) were administered two intramuscular immunizations (21 days apart) of PBS control or LNP-formulated mRNA vaccines including 10 μg of a bivalent mRNA-native vaccine encoding the ancestral D614G and Omicron BA.4/5 spike proteins, and either 10 or 2 μg of the bivalent mRNA-VLP vaccine encoding the D614G spike VLP and Omicron BA.4/5 spike VLP. Fourteen days following the second immunization, sera were collected for pseudovirus-based neutralization assays. On study day 42, hamsters were challenged intranasally with ancestral SARS-CoV-2 virus and then weighed and monitored daily. One cohort of hamsters from each group (n = 8) was euthanized on study day 45 (three days post virus challenge), which correlates with peak virological measurements. A second cohort of hamsters from each group (n = 8) was euthanized on study day 49 (seven days post virus challenge), which correlates with peak pathological findings associated with SARS-CoV-2 infection. B The geometric mean neutralizing antibody titer (GMT) ± geometric standard deviation is shown for both ancestral D614G and Omicron BA.4/5 pseudoviruses; dotted horizontal line indicates the assay lower limit of detection (LLD). C Mean percent change in body weights (relative to weights recorded on day 42 prior to challenge) and standard deviation post virus challenge. D Oral swabs collected on day 2 post virus challenge were assessed for viral sgRNA concentrations by qRT-PCR. E Lung homogenates collected on days 3 and 7 post virus challenge were assessed for infectious virus by TCID50 assay. F Lung homogenates collected on days 3 and 7 post virus challenge were assessed for viral sgRNA concentrations by qRT-PCR. Data represent geometric means ± geometric standard deviations; dotted horizontal line indicates the assay LLD. p values comparing the different vaccine group responses are indicated as determined by Kruskal–Wallis test. ID50 half-maximal inhibitory dilution, ns not significant, PBS phosphate-buffered saline, qRT-PCR quantitative real-time polymerase chain reaction, sgRNA subgenomic RNA, *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.