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iScience . Intranasal murine pneumonia virus-vectored SARS-CoV-2 vaccine induces mucosal and serum antibodies in macaques

tetano

Editor, Senior Moderator
iScience


. 2023 Nov 22;26(12):108490.
doi: 10.1016/j.isci.2023.108490. eCollection 2023 Dec 15. Intranasal murine pneumonia virus-vectored SARS-CoV-2 vaccine induces mucosal and serum antibodies in macaques

Jaclyn A Kaiser[SUP] 1 [/SUP], Xueqiao Liu[SUP] 1 [/SUP], Cindy Luongo[SUP] 1 [/SUP], Yumiko Matsuoka[SUP] 1 [/SUP], Celia Santos[SUP] 1 [/SUP], Lijuan Yang[SUP] 1 [/SUP], Richard Herbert[SUP] 2 [/SUP], Ashley Castens[SUP] 2 [/SUP], David W Dorward[SUP] 3 [/SUP], Reed F Johnson[SUP] 4 [/SUP], Hong-Su Park[SUP] 1 [/SUP], Sharmin Afroz[SUP] 1 [/SUP], Shirin Munir[SUP] 1 [/SUP], Cyril Le Nouën[SUP] 1 [/SUP], Ursula J Buchholz[SUP] 1 [/SUP]



Affiliations
Abstract

Next-generation SARS-CoV-2 vaccines are needed that induce systemic and mucosal immunity. Murine pneumonia virus (MPV), a murine homolog of respiratory syncytial virus, is attenuated by host-range restriction in nonhuman primates and has a tropism for the respiratory tract. We generated MPV vectors expressing the wild-type SARS-CoV-2 spike protein (MPV/S) or its prefusion-stabilized form (MPV/S-2P). Both vectors replicated similarly in cell culture and stably expressed S. However, only S-2P was associated with MPV particles. After intranasal/intratracheal immunization of rhesus macaques, MPV/S and MPV/S-2P replicated to low levels in the airways. Despite its low-level replication, MPV/S-2P induced high levels of mucosal and serum IgG and IgA to SARS-CoV-2 S or its receptor-binding domain. Serum antibodies from MPV/S-2P-immunized animals efficiently inhibited ACE2 receptor binding to S proteins of variants of concern. Based on its attenuation and immunogenicity in macaques, MPV/S-2P will be further evaluated as a live-attenuated vaccine for intranasal immunization against SARS-CoV-2.

Keywords: Immune response; Immunology; Virology.

 
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