# Boost and Increased Antibody Breadth Following a Second Dose of PARVAX for SARS-CoV-2 in Mice and Nonhuman Primates

## TL;DR

This study shows that a second dose of the PARVAX vaccine can boost antibody responses in mice and nonhuman primates, with varying effectiveness depending on the antigen used.

## Contribution

The study demonstrates the potential of re-administering the PARVAX vaccine to induce new antigenic responses and increase antibody breadth.

## Key findings

- A low-dose prime followed by a higher-dose boost in mice elicited potent neutralizing antibody responses.
- Boosting NHPs with an Omicron BA.1 vaccine increased antibodies against several Omicron variants.
- Anti-vector antibody responses in mice limited the prime dose and declined over time in NHPs.

## Abstract

PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, a low-dose prime followed by a higher-dose boost elicited potent neutralizing antibody responses and distinct cross-reactivity profiles, depending on the antigen used in the booster vaccine. However, the potent neutralizing anti-vector antibody responses developed in mice limited the dose that could be administered as a prime. We further explored the re-administration efficacy in NHPs primed with a SARS-CoV-2 Delta vaccine and boosted with an Omicron BA.1 vaccine at week 15, after the primary response peak antibody levels were reached. The boost elicited an increase in antibodies against several Omicron variants, but no increase was detected in the antibody titers for other variants. The anti-vector responses were low and showed some increased subsequent boosts but generally declined over time. The potent prime vaccination limited the detection of the boosting effect, and therefore, the effect of anti-vector immunity was not fully elucidated. These data show that PARVAX can be effectively re-administered and induce a novel antigenic response.