Influenza Vaccines

Influenza A virus infections cause 3–5 million cases of severe illness and about 250,000–500,000 deaths across the globe every year. In addition, highly pathogenic strains of the virus occasionally emerge that are associated with particularly high mortality rates. Current vaccines are modestly effective, but the underlying technologies are not optimal for responding rapidly to highly pathogenic pandemics. In this context, several articles in the current issue of Viral Immunology address various vaccination strategies against influenza virus. Seo and Kim point out that the H7N9 influenza virus, which emerged in China 3 years ago, is highly pathogenic with a human mortality rate of 20%. The development of an effective vaccine against this influenza strain is a priority. To address this problem, the authors have generated an H7N9 vaccine virus with six internal genes of A/PR/8/34 (H1N1) and two surface genes of hemagglutinin (HA) and neuraminidase from A/Anhui/1/2013 (H7N9) by reverse genetics. Mice immunized with a single dose of the H7N9 vaccine were protected against a lethal challenge with the H7N9 virus. These data suggest that the vaccine could be developed to protect animals and humans from its lethal infection.

In a similar study, Ameghi et al. developed recombinant chimeric fusion peptides of HA2 and M2e from influenza virus A/Brisbane/59/2007-like (H1N1). Vaccination of mice with the chimeric peptide induced strong protection against homologous virus challenge and weaker protection against heterologous virus challenge. The authors speculate that this vaccine may be broadly protective against other viral strains, but caution that more studies are needed to optimize this vaccine candidate.

It is well known that neutralizing antibodies to the HA coat proteins of influenza A viruses mediate strong protection against antigenically matched strains of the virus. However, Zhong et al. point out that little is known about the potential role of HA-specific, non-neutralizing antibodies in protection against influenza. To address this question, the authors analyze sera from individuals vaccinated with the 2014–2015 seasonal inactivated influenza vaccine for their protective efficacy. The data indicate that serum antibodies displayed strong antiviral activities against an antigenically drifted influenza virus despite poor induction of cross-reactive neutralizing antibodies against the antigenic variant. These findings, which are supported by animal models, suggest that that HA-specific, non-neutralizing antibodies may provide cross-protection against antigenically drifted influenza A viruses and have important implications for public health.

Influenza is also a significant problem for veterinary medicine. Hasan et al. note that vaccination plays a role in eradicating avian influenza viruses from commercial poultry, especially in countries where avian influenza is endemic. One of the challenges of this approach is that conventional serological tests fail to differentiate antibodies produced because of vaccination from antibodies produced in response to virus infection. This poses significant problems for regulatory authorities. Several different vaccine strategies have been used to address this problem. The authors review these strategies and discuss the feasibility and practicality of the options as a part of the surveillance program directed toward the eventual eradication of avian influenza.

One article in the current issue of Viral Immunology does not specifically address vaccines, but discusses the role of microRNAs (miRNAs) in regulating the immune response to influenza A viral infections. Rivera et al. have conducted a comprehensive analysis of innate and adaptive immune responses as well as the expression of several miRNA and their validated targets in both peripheral blood and bronchoalveolar lavage collected from rhesus macaques over the course of infection with the 2009 H1N1 virus A/Mexico/4108/2009. The data indicate that a distinct set of differentially expressed miRNAs regulates the expression of genes involved in inflammation, immune responses, and regulation of cell cycle and apoptosis. These data have implications for developing future therapeutics against influenza virus infection.

Finally, two additional articles in this issue address immunity to two other viruses: hepatitis C virus (HCV) and classical swine fever virus (CSFV). Abdel-Hameed et al. evaluate the impact of cellular immune responses on the emergence of HCV protease-resistance mutations in chronically HCV-infected subjects treated with Boceprevir-based triple therapy. The data suggest that strong NS3-specific T-cell immune responses may predict a positive outcome of antiviral therapy. Li et al. have developed a CSFV vaccine and tested it in pigs. Their data show that the vaccine induced strong humoral and cellular responses and resulted in complete protection against lethal CSFV infection. The authors argue that this could be a promising virus for CSFV infection.

I would like to thank all of the authors for their excellent contributions to this issue of Viral Immunology and all of the reviewers for their efforts in ensuring the quality of published articles.