Off-target effects of an insect cell-expressed influenza HA-pseudotyped Gag-VLP preparation in limiting postinfluenza Staphylococcus aureus infections

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Vaccine. 2019 Nov 9. pii: S0264-410X(19)31472-0. doi: 10.1016/j.vaccine.2019.10.083. [Epub ahead of print] Off-target effects of an insect cell-expressed influenza HA-pseudotyped Gag-VLP preparation in limiting postinfluenza Staphylococcus aureus infections.

Klausberger M¹, Leneva IA², Egorov A³, Strobl F⁴, Ghorbanpour SM⁴, Falynskova IN², Poddubikov AV⁵, Makhmudova NR², Krokhin A⁶, Svitich OA², Grabherr R⁶.
Author information

1 Department of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria. Electronic address: Miriam.klausberger@boku.ac.at. 2 Department of Virology, I. Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia. 3 Department of Virology, I. Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia; Smorodintsev Research Institute of Influenza, Saint-Petersburg, Russia. 4 Austrian Centre of Industrial Biotechnology (ACIB), Vienna, Austria. 5 Department of Microbiology, I. Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia. 6 Department of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.

Abstract

Clinical and historical data underscore the ability of influenza viruses to ally with Staphylococcus aureus and predispose the host for secondary bacterial pneumonia, which is a leading cause of influenza-associated mortality. This is fundamental because no vaccine for S. aureus is available and the number of antibiotic-resistant strains is alarmingly rising. Hence, this leaves influenza vaccination the only strategy to prevent postinfluenza staphylococcal infections. In the present work, we assessed the off-target effects of a Tnms42 insect cell-expressed BEI-treated Gag-VLP preparation expressing the HA of A/Puerto Rico/8/1934 (H1N1) in preventing S. aureus superinfection in mice pre-infected with a homologous or heterologous H1N1 viral challenge strain. Our results demonstrate that matched anti-hemagglutinin immunity elicited by a VLP preparation may suffice to prevent morbidity and mortality caused by lethal secondary bacterial infection. This effect was observed even when employing a single low antigen dose of 50 ng HA per animal. However, induction of anti-hemagglutinin immunity alone was not helpful in inhibiting heterologous viral replication and subsequent bacterial infection. Our results indicate the potential of the VLP vaccine approach in terms of immunogenicity but suggest that anti-HA immunity should not be considered as the sole preventive method for combatting influenza and postinfluenza bacterial infections.
Copyright ? 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.


KEYWORDS:

Influenza; Secondary bacterial infection; Staphylococcus aureus; VLP vaccine; Vaccine off-target effects

PMID: 31718898 DOI: 10.1016/j.vaccine.2019.10.083