Protection against SARS-CoV-2 transmission by a parenteral prime-Intranasal boost vaccine strategy.

Background: Licensed vaccines against SARS-CoV-2 effectively protect against severe disease, but display incomplete protection against virus transmission. Mucosal vaccines providing immune responses in the upper airways are one strategy to protect against transmission.
Methods: We administered Spike HexaPro trimer formulated in a cationic liposomal adjuvant as a parenteral (subcutaneous - s.c.) prime - intranasal boost regimen to elicit airway mucosal immune responses and evaluated this in a Syrian hamster model of virus transmission.
Findings: Parenteral prime - intranasal boost elicited high-magnitude serum neutralizing antibody responses and IgA responses in the upper respiratory tract. The vaccine strategy protected against virus in the lower airways and lung pathology, but virus could still be detected in the upper airways. Despite this, the parenteral prime - intranasal booster vaccine effectively protected against onward SARS-CoV-2 transmission.
Interpretation: This study suggests that parenteral-prime mucosal boost is an effective strategy for protecting against SARS-CoV-2 infection and highlights that protection against virus transmission may be obtained despite incomplete clearance of virus from the upper respiratory tract. It should be noted that protection against onward transmission was not compared to standard parenteral prime-boost, which should be a focus for future studies.
Funding: This work was primarily supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 101003653.
Competing Interests: Declaration of interests D.C. is co-inventor on patents on the cationic adjuvant formulations (CAF). All rights have been turned over to Statens Serum Institut, which is a non-profit government research facility. The rest of the authors declare that there are no competing interests.
(Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)