Development of a Novel Live Attenuated Influenza A Virus Vaccine Encoding the IgA-Inducing Protein

C. Joaquín Cáceres; Stivalis Cardenas-Garcia; Aarti Jain; L. Claire Gay; Silvia Carnaccini; Brittany Seibert; Lucas M. Ferreri; Ginger Geiger; Algimantas Jasinskas; Rie Nakajima; Daniela S. Rajao; Irina Isakova-Sivak; Larisa Rudenko; Amy L. Vincent; D. Huw Davies; Daniel R. Perez

doi:10.3390/vaccines9070703

Vaccines (Jun 2021)

Development of a Novel Live Attenuated Influenza A Virus Vaccine Encoding the IgA-Inducing Protein

C. Joaquín Cáceres,
Stivalis Cardenas-Garcia,
Aarti Jain,
L. Claire Gay,
Silvia Carnaccini,
Brittany Seibert,
Lucas M. Ferreri,
Ginger Geiger,
Algimantas Jasinskas,
Rie Nakajima,
Daniela S. Rajao,
Irina Isakova-Sivak,
Larisa Rudenko,
Amy L. Vincent,
D. Huw Davies,
Daniel R. Perez

Affiliations

C. Joaquín Cáceres: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
Stivalis Cardenas-Garcia: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
Aarti Jain: Department of Physiology and Biophysics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA
L. Claire Gay: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
Silvia Carnaccini: Tifton Diagnostic Laboratory, College of Veterinary Medicine, University of Georgia, Tifton, GA 31793, USA
Brittany Seibert: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
Lucas M. Ferreri: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
Ginger Geiger: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
Algimantas Jasinskas: Department of Physiology and Biophysics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA
Rie Nakajima: Department of Physiology and Biophysics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA
Daniela S. Rajao: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
Irina Isakova-Sivak: Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street, 197376 St Petersburg, Russia
Larisa Rudenko: Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street, 197376 St Petersburg, Russia
Amy L. Vincent: National Animal Disease Center, USDA-ARS, 1920 Dayton Avenue, Ames, IA 50010, USA
D. Huw Davies: Department of Physiology and Biophysics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA
Daniel R. Perez: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA

DOI: https://doi.org/10.3390/vaccines9070703
Journal volume & issue: Vol. 9, no. 7
p. 703

Abstract

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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, the introduction of genes encoding immunomodulatory functions into a candidate LAIV can serve as natural adjuvants to improve overall vaccine safety and efficacy.

Published in Vaccines

ISSN: 2076-393X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine
Website: http://www.mdpi.com/journal/vaccines

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