Recombinant PIV5 vaccine encoding the influenza hemagglutinin protects against H5N1 highly pathogenic avian influenza virus infection following intranasal or intramuscular vaccination of BALB/c mice.
ABSTRACT New approaches for vaccination to prevent influenza virus infection are needed. Emerging viruses, such as H5N1 highly pathogenic avian influenza (HPAI) virus, pose not only pandemic threats, but also challenges in vaccine development and production. Parainfluenza virus 5 (PIV5) is an appealing vector for vaccine development and we have previously shown that intranasal immunization with PIV5 expressing the hemagglutinin from influenza virus was protective against influenza virus challenge. While intranasal immunization is an appealing approach, PIV5 may have potential to be utilized in other formats, prompting us to test the efficacy of rPIV5-H5, which encodes the HA from H5N1 HPAI virus, in different vaccination schemes. In the BALB/c mouse model, a single intramuscular or intranasal immunization with a live rPIV5-H5 (ZL46) rapidly induced robust neutralizing serum antibody responses and protected against HPAI challenge, although mucosal IgA responses primed by intranasal immunization more effectively controlled virus replication in the lung. The rPIV5-H5 vaccine incorporated the H5 HA into the virion, and so we tested the efficacy of an inactivated format of the vaccine. Inactivated rPIV5-H5 primed neutralizing serum antibody responses and controlled H5N1 virus replication, although similar to other H5 antigen vaccines, it required a booster immunization to prime protective immune responses. Taken together, these results suggest that rPIV5-HA vaccines and H5-specific vaccines in particular, may be utilized in multiple formats and by multiple routes of administration. This could avoid potential contraindications based upon intranasal administration alone and provide opportunities for broader applications, with the use of a single vaccine vector.
SourceAvailable from: John Wilson Finger[Show abstract] [Hide abstract]
ABSTRACT: Abstract Avian influenza has emerged as one of the most ubiquitous viruses within our biosphere. Wild aquatic birds are believed to be the primary reservoir of all influenza viruses; however, the spillover of H5N1 highly pathogenic avian influenza (HPAI) and the recent swine-origin pandemic H1N1 viruses have sparked increased interest in identifying and understanding which and how many species can be infected. Moreover, novel influenza virus sequences were recently isolated from New World bats. Crocodilians have a slow rate of molecular evolution and are the sister group to birds; thus they are a logical reptilian group to explore susceptibility to influenza virus infection and they provide a link between birds and mammals. A primary American alligator (Alligator mississippiensis) cell line, and embryos, were infected with four, low pathogenic avian influenza (LPAI) strains to assess susceptibility to infection. Embryonated alligator eggs supported virus replication, as evidenced by the influenza virus M gene and infectious virus detected in allantoic fluid and by virus antigen staining in embryo tissues. Primary alligator cells were also inoculated with the LPAI viruses and showed susceptibility based upon antigen staining; however, the requirement for trypsin to support replication in cell culture limited replication. To assess influenza virus replication in culture, primary alligator cells were inoculated with H1N1 human influenza or H5N1 HPAI viruses that replicate independent of trypsin. Both viruses replicated efficiently in culture, even at the 30 C temperature preferred by the alligator cells. This research demonstrates the ability of wild-type influenza viruses to infect and replicate within two crocodilian substrates and suggests the need for further research to assess crocodilians as a species potentially susceptible to influenza virus infection.Journal of wildlife diseases 01/2015; 51(1):187-198. DOI:10.7589/2013-12-321 · 1.31 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The increasing outbreaks of highly pathogenic avian influenza A (HPAI) H5N1 viruses in birds and human bring out an urgent need to develop a safe and effective vaccine to control and prevent H5N1 infection. Lactococcus lactis (L. lactis) based vaccine platform is a promising approach for mucosal H5N1 vaccine development. Intranasal immunization is the potential to induce mucosal immune response which is associated with protective immunity. To develop a safe and effective mucosal vaccine against HAPI H5N1, we extended our previous study by evaluating the immunogenicity of L. lactis-psA-HA1 in the absence of adjuvant via intranasal route in the ferret model. Ferrets administered intranasally with L. lactis-pgsA-HA1 could elicit robust humoral and mucosal immune responses, as well as significant HI titers. Importantly, ferrets were completely protected from H5N1 virus challenge. These findings suggest that L. lactis-pgsA-HA1 can be considered an alternative mucosal vaccine during A/H5N1 pandemic. Copyright © 2014 Elsevier B.V. All rights reserved.Virus Research 11/2014; 196C:56-59. DOI:10.1016/j.virusres.2014.11.009 · 2.83 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic.PLoS ONE 01/2015; 10(2):e0115725. DOI:10.1371/journal.pone.0115725 · 3.53 Impact Factor