RT Journal Article
SR Electronic
T1 An intranasal lentiviral booster broadens immune recognition of SARS-CoV-2 variants and reinforces the waning mRNA vaccine-induced immunity that it targets to lung mucosa
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.30.478159
DO 10.1101/2022.01.30.478159
A1 Benjamin Vesin
A1 Jodie Lopez
A1 Amandine Noirat
A1 Pierre Authié
A1 Ingrid Fert
A1 Fabien Le Chevalier
A1 Fanny Moncoq
A1 Kirill Nemirov
A1 Catherine Blanc
A1 Cyril Planchais
A1 Hugo Mouquet
A1 Françoise Guinet
A1 David Hardy
A1 Christiane Gerke
A1 François Anna
A1 Maryline Bourgine
A1 Laleh Majiessi
A1 Pierre Charneau
YR 2022
UL http://biorxiv.org/content/early/2022/01/31/2022.01.30.478159.abstract
AB As the COVID-19 pandemic continues and new SARS-CoV-2 variants of concern emerge, the adaptive immunity initially induced by the first-generation COVID-19 vaccines wains and needs to be strengthened and broadened in specificity. Vaccination by the nasal route induces mucosal humoral and cellular immunity at the entry point of SARS-CoV-2 into the host organism and has been shown to be the most effective for reducing viral transmission. The lentiviral vaccination vector (LV) is particularly suitable for this route of immunization because it is non-cytopathic, non-replicative and scarcely inflammatory. Here, to set up an optimized cross-protective intranasal booster against COVID-19, we generated an LV encoding stabilized Spike of SARS-CoV-2 Beta variant (LV::SBeta-2P). mRNA vaccine–primed and -boosted mice, with waning primary humoral immunity at 4 months post-vaccination, were boosted intranasally with LV::SBeta-2P. Strong boost effect was detected on cross-sero-neutralizing activity and systemic T-cell immunity. In addition, mucosal anti-Spike IgG and IgA, lung resident B cells, and effector memory and resident T cells were efficiently induced, correlating with complete pulmonary protection against the SARS-CoV-2 Delta variant, demonstrating the suitability of the LV::SBeta-2P vaccine candidate as an intranasal booster against COVID-19.Competing Interest StatementPC is the founder and CSO of TheraVectys. BV, AN, PA, IF, FLC, FM, KN and FA are employees of TheraVectys. LM has a consultancy activity for TheraVectys. Other authors declare no competing interests. PA, IF, JL, BV, FA, MB, LM and PC are inventors of pending patents directed to the potential of i.n. LV::S vaccination against SARS-CoV-2.