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Volume 9
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Article

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

by
C. Joaquín Cáceres
1,
Stivalis Cardenas-Garcia
1,
Aarti Jain
2,
L. Claire Gay
1,
Silvia Carnaccini
3,
Brittany Seibert
1,
Lucas M. Ferreri
1,
Ginger Geiger
1,
Algimantas Jasinskas
2,
Rie Nakajima
2,
Daniela S. Rajao
1,
Irina Isakova-Sivak
4,
Larisa Rudenko
4,
Amy L. Vincent
5,
D. Huw Davies
2 and
Daniel R. Perez
1,*
1
Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
2
Department of Physiology and Biophysics, School of Medicine, University of California Irvine, Irvine, CA 92697, USA
3
Tifton Diagnostic Laboratory, College of Veterinary Medicine, University of Georgia, Tifton, GA 31793, USA
4
Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street, 197376 St Petersburg, Russia
5
National Animal Disease Center, USDA-ARS, 1920 Dayton Avenue, Ames, IA 50010, USA
*
Author to whom correspondence should be addressed.
Vaccines 2021, 9(7), 703; https://doi.org/10.3390/vaccines9070703
Submission received: 28 May 2021 / Revised: 19 June 2021 / Accepted: 22 June 2021 / Published: 27 June 2021
(This article belongs to the Special Issue Progress on Seasonal and Pandemic Influenza Vaccines)
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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, the introduction of genes encoding immunomodulatory functions into a candidate LAIV can serve as natural adjuvants to improve overall vaccine safety and efficacy.
Keywords: LAIV; influenza; HA; IGIP; IgA; IgG; vaccine; natural adjuvant LAIV; influenza; HA; IGIP; IgA; IgG; vaccine; natural adjuvant

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MDPI and ACS Style

Cáceres, C.J.; Cardenas-Garcia, S.; Jain, A.; Gay, L.C.; Carnaccini, S.; Seibert, B.; Ferreri, L.M.; Geiger, G.; Jasinskas, A.; Nakajima, R.; et al. Development of a Novel Live Attenuated Influenza A Virus Vaccine Encoding the IgA-Inducing Protein. Vaccines 2021, 9, 703. https://doi.org/10.3390/vaccines9070703

AMA Style

Cáceres CJ, Cardenas-Garcia S, Jain A, Gay LC, Carnaccini S, Seibert B, Ferreri LM, Geiger G, Jasinskas A, Nakajima R, et al. Development of a Novel Live Attenuated Influenza A Virus Vaccine Encoding the IgA-Inducing Protein. Vaccines. 2021; 9(7):703. https://doi.org/10.3390/vaccines9070703

Chicago/Turabian Style

Cáceres, C. Joaquín, Stivalis Cardenas-Garcia, Aarti Jain, L. Claire Gay, Silvia Carnaccini, Brittany Seibert, Lucas M. Ferreri, Ginger Geiger, Algimantas Jasinskas, Rie Nakajima, and et al. 2021. "Development of a Novel Live Attenuated Influenza A Virus Vaccine Encoding the IgA-Inducing Protein" Vaccines 9, no. 7: 703. https://doi.org/10.3390/vaccines9070703

APA Style

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. (2021). Development of a Novel Live Attenuated Influenza A Virus Vaccine Encoding the IgA-Inducing Protein. Vaccines, 9(7), 703. https://doi.org/10.3390/vaccines9070703

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