Efficacy of a parainfluenza virus 5 (PIV5)-based H7N9 vaccine in mice and guinea pigs: antibody titer towards HA was not a good indicator for protection.

Zhuo Li,Daniel Dlugolenski,Shannon Phan,Scott Johnson,Biao He,Jon D Gabbard,S Mark Tompkins,Moriya Tsuji

doi:10.1371/journal.pone.0120355

Abstract

H7N9 has caused fatal infections in humans. A safe and effective vaccine is the best way to prevent large-scale outbreaks in the human population. Parainfluenza virus 5 (PIV5), an avirulent paramyxovirus, is a promising vaccine vector. In this work, we generated a recombinant PIV5 expressing the HA gene of H7N9 (PIV5-H7) and tested its efficacy against infection with influenza virus A/Anhui/1/2013 (H7N9) in mice and guinea pigs. PIV5-H7 protected the mice against lethal H7N9 challenge. Interestingly, the protection did not require antibody since PIV5-H7 protected JhD mice that do not produce antibody against lethal H7N9 challenge. Furthermore, transfer of anti-H7 serum did not protect mice against H7N9 challenge. PIV5-H7 generated high HAI titers in guinea pigs, however it did not protect against H7N9 infection or transmission. Intriguingly, immunization of guinea pigs with PIV5-H7 and PIV5 expressing NP of influenza A virus H5N1 (PIV5-NP) conferred protection against H7N9 infection and transmission. Thus, we have obtained a H7N9 vaccine that protected both mice and guinea pigs against lethal H7N9 challenge and infection respectively.

Highlights

Influenza virus is a segmented, negative strand, RNA virus belonging to the Orthomyxoviridae family [1]
Survival was significantly different in Parainfluenza virus 5 (PIV5)-H7 immunized mice compared to either PBS or PIV5 control groups (P
It is interesting that inactivated H7N9, even at 10 times of normal amount, did not generate detectable HAI titer in mice (Fig. 4), yet it was protective of mice against lethal H7N9 challenge

Summary

Introduction

Influenza virus is a segmented, negative strand, RNA virus belonging to the Orthomyxoviridae family [1]. Influenza viruses are classified into three families, types A, B, and C, with types A and C infecting a variety of species, including humans and birds, and type B infecting primarily humans. Influenza A virus is associated with pandemics. Influenza A virus is classified by its two major surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). There are 18 HA and 11 NA subtypes, differing by ! 30% in protein sequence similarity, which are used to categorize influenza A virus into subtypes (e.g. H1N1, H3N2, H5N1, etc.) [2,3,4]. The first wave of infection and fatality cases in humans by avian influenza A virus H7N9 were reported

Methods

Results

Conclusion