Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Development of a novel Live Attenuated Influenza A Virus vaccine encoding the IgA-inducing protein

C. Joaquín Cáceres
ORCID logo ,
Stivalis Cardenas-Garcia
ORCID logo ,
Aarti Jain
,
L. Claire Gay
,
Silvia Carnaccini
,
Brittany Seibert
,
Lucas M Ferreri
,
Ginger Geiger
ORCID logo ,
Alguimantas Jasinskas
,
Rie Nakajima
,
Daniela S Rajao
ORCID logo ,
Irina Isakova-Sivak
,
Larisa Rudenko
,
Amy L Vincent
,
D. Huw Davies
,
Daniel R Perez
*
Version 1 : Received: 4 June 2021 / Approved: 7 June 2021 / Online: 7 June 2021 (13:03:43 CEST)

A peer-reviewed article of this Preprint also exists.

Cáceres, C.J.; Cardenas-Garcia, S.; Jain, A.; Gay, L.C.; Carnaccini, S.; Seibert, B.; Ferreri, L.M.; Geiger, G.; Jasinskas, A.; Nakajima, R.; Rajao, D.S.; Isakova-Sivak, I.; Rudenko, L.; Vincent, A.L.; Davies, D.H.; Perez, D.R. Development of a Novel Live Attenuated Influenza A Virus Vaccine Encoding the IgA-Inducing Protein. Vaccines 2021, 9, 703. Cáceres, C.J.; Cardenas-Garcia, S.; Jain, A.; Gay, L.C.; Carnaccini, S.; Seibert, B.; Ferreri, L.M.; Geiger, G.; Jasinskas, A.; Nakajima, R.; Rajao, D.S.; Isakova-Sivak, I.; Rudenko, L.; Vincent, A.L.; Davies, D.H.; Perez, D.R. Development of a Novel Live Attenuated Influenza A Virus Vaccine Encoding the IgA-Inducing Protein. Vaccines 2021, 9, 703.

Abstract

Live attenuated influenza virus (LAIV) vaccines elicit a combination of systemic and mucosal immunity by mimicking a natural infection. To further enhance protective mucosal responses, we incorporated the gene encoding the IgA-inducing protein (IGIP) into the LAIV genomes of the cold-adapted A/Leningrad/134/17/57 (H2N2) strain (caLen) and the experimental attenuated backbone A/turkey/Ohio/313053/04 (H3N2) (OH/04att). Incorporation of IGIP into the caLen background led to a virus that grew poorly in prototypical substrates. In contrast, IGIP in the OH/04att background (IGIP-H1att) virus grew to titers comparable to the isogenic backbone H1att (H1N1) without IGIP. IGIP-H1att- and H1caLen-vaccinated mice were protected against lethal challenge with a homologous virus. The IGIP-H1att vaccine generated robust serum HAI responses in naïve mice against the homologous virus, equal or better than those obtained with the H1caLen vaccine. Analyses of IgG and IgA responses using a protein microarray revealed qualitative differences in humoral and mucosal responses between vaccine groups. Overall, serum and bronchoalveolar lavage samples from the IGIP-H1att group showed trends towards increased stimulation of IgG and IgA responses compared to H1caLen samples. In summary, introduction of genes encoding immunomodulatory functions into a candidate LAIV that can serve as natural adjuvants to improve overall vaccine safety and efficacy.

Keywords

LAIV, Influenza, HA, IGIP, IgA, IgG, vaccine, natural adjuvant

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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