Antibody Responses to Influenza A Virus Infection

Influenza A virus is a very significant human pathogen responsible for both seasonal epidemics, characterized by severe illness and up to 500,000 deaths per year, and pandemics, which can cause millions of deaths in a given year. Current vaccines have limited efficacy against influenza, especially in the elderly, and the available anti-influenza drugs have severe limitations. Moreover, there is much that we still need to learn about protective immunity against the virus. For example, it is clear that antibody responses can play a key role in protective immunity, but the underlying mechanisms of protection are not fully understood.

In the current issue of Viral Immunology, two papers directly address the role of antibodies in the control of influenza A virus infection. Co et al. point out that although the hemagglutination inhibition (HAI) antibody titer is considered the primary immune correlate of protection for influenza, there are limitations to this assay in at-risk populations, such as children and older adults. Importantly, this assay does not distinguish between the roles of antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent lysis (CDL). The authors address this issue by evaluating preexisting HAI, CDL, and ADCC antibodies in young children during the epidemic with influenza A(H1N1)pdm09 virus. The data indicate that preexisting HAI and CDL antibodies, but not ADCC antibodies, were associated with protection against influenza. This is the first study to examine the relationship between preexisting HAI, CDL, and ADCC antibodies and the subsequent development of clinical influenza in young children. The authors note that confirmation of these results in a larger prospective study, including age-matched children and adult subjects, is needed. In a second study, Kumagai et al. examined the role of humoral immunity in the kinetics of HAI, neutralization, and the IgG subclass antibody response directed against the same influenza A(H1N1)pdm2009 virus or against vaccination. They showed that the titers of HAI and neutralizing antibodies were low during the acute phase of the infection, and peaked around 4 weeks after symptom onset. In contrast, IgG3 antibody titers peaked around 2 weeks after vaccination. Taken together, these two studies advance our understanding of the humoral response to influenza and provide information that might be useful for future vaccine development.

Several papers in this issue of Viral Immunology address different aspects of the inflammatory response to viral infection. Okino et al. investigated the inflammatory and cell-mediated immune responses in the respiratory tract of chickens to infection with avian Infectious Bronchitis Virus (IBV). The data suggest that the rapid expression of pro-inflammatory cytokines such as IL-6, IL-1β and IFN-γ and the late induction of CD8αα and granzyme homolog A genes play a key role in viral pathogenicity of IBV infection. Many pro- and anti-inflammatory cytokines are made by dendritic cells. In this regard, Agrawal et al. investigated the combined effects of hepatitis B and C virus core proteins on the capacity of human dendritic cells to present antigens and stimulate antigen-specific T-cells. They found that the viral proteins resulted in (i) dramatically enhanced IL-10 production, (ii) significantly reduced IL-6, TNF-α, and IL-12 production, and (iii) downregulated HLA-DR expression in the dendritic cells. This caused them to have tolerogenic effects by inefficiently presenting antigens to CD4+ T-cells and suppressing the induction of the cellular immune response. Imran et al. analyzed the genetic variation of the locus encoding the pro-inflammatory cytokine, IL18, in HCV-infected Pakistani patients undergoing interferon plus ribavirin treatment. Their data suggest that IL-18-related polymorphisms may be associated with the clearance of HCV infection. Along the same lines, Sepahi et al. found a possible association between IL-10 promoter polymorphisms and HCV infection, and note that certain genotypes may confer a higher risk or susceptibility for developing HCV infection.

Two important aspects of viral infections are the development of therapeutic drug resistance and the secondary side effects of virally induced illnesses. Dai et al. analyzed transmitted antiretroviral drug resistance to HIV in men who have sex with men in a Beijing cohort. Their study provides important insights for public health planning in China. Xiang et al. present a case report of Guillain–Barré syndrome associated with Japanese encephalitis virus infection in China. The authors note that prompt diagnosis of Guillain–Barré syndrome is important, given the beneficial effects of intravenous immunoglobulin or plasma exchange.

I would like to thank all of the authors and reviewers for contributing to another excellent issue of Viral Immunology.