In most cases, the pandemic H1N1 2009 influenza virus (pH1N1) strain is self-limiting and mirrors infection by commonly circulating seasonal influenza virus strains. However, pregnant and postpartum women are at greater risk for severe clinical manifestations (20,44,47,73). In one study, the Centers for Disease Control and Prevention reported a death rate of 20% in pregnant women in the United States who were hospitalized with pH1N1-related symptoms (72). Among these deaths, 64% occurred within the third trimester of pregnancy. Serious influenza-induced complications in pregnant women are not a new phenomenon. In sharp contrast to the general population, pregnant women had disproportionately high rates of hospital admission and mortality during the previous influenza pandemics: the

SUMMARY Vaccines are instrumental in controlling the burden of influenza virus infection in humans and animals. Antibodies raised against both major viral surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), can contribute to protective immunity. Vaccine‐induced HA antibodies have been characterized extensively, and they generally confer protection by blocking the attachment and fusion of a homologous virus onto host cells. Although not as well characterized, some functions of NA antibodies in influenza vaccine‐mediated immunity have been recognized for many years. In this review, we summarize the case for NA antibodies in influenza vaccine‐mediated immunity. In the absence of well‐matched HA antibodies, NA antibodies can provide varying degrees of protection against disease. NA proteins of seasonal influenza vaccines have been shown in some instances to elicit serum antibodies with cross‐reactivity to avian‐origin and swine‐origin influenza strains, in addition to HA drift variants. NA‐mediated immunity has been linked to (i) conserved NA epitopes amongst otherwise antigenically distinct strains, partly attributable to the segmented influenza viral genome; (ii) inhibition of NA enzymatic activity; and (iii) the NA content in vaccine formulations. There is a potential to enhance the effectiveness of existing and future influenza vaccines by focusing greater attention on the antigenic characteristics and potency of the NA protein. Copyright © 2012 John Wiley & Sons, Ltd.

Pre-existing antibodies to the hemagglutinin of pandemic A (H1N1) 2009 influenza virus (pH1N1) positively correlates with age. The impact of contemporary seasonal influenza vaccines on establishing immunity to other pH1N1 proteins is unknown. We measured serum antibodies to the neuraminidase of pandemic H1N1 (pNA) in adults prior to and after vaccination with seasonal trivalent inactivated influenza vaccines. Serum antibodies to pNA were observed in all age groups; however, vaccination elevated pNA antibodies in predominately the elderly. Therefore, contemporary seasonal vaccines likely contribute to reduction of pH1N1 associated disease in older individuals.

BackgroundExposure to contemporary seasonal influenza A viruses affords partial immunity to pandemic H1N1 2009 influenza A virus (pH1N1) infection. The impact of antibodies to the neuraminidase (NA) of seasonal influenza A viruses to cross-immunity against pH1N1 infection is unknown.Methods and ResultsAntibodies to the NA of different seasonal H1N1 influenza strains were tested for cross-reactivity against A/California/04/09 (pH1N1). A panel of reverse genetic (rg) recombinant viruses was generated containing 7 genes of the H1N1 influenza strain A/Puerto Rico/08/34 (PR8) and the NA gene of either the pandemic H1N1 2009 strain (pH1N1) or one of the following contemporary seasonal H1N1 strains: A/Solomon/03/06 (rg Solomon) or A/Brisbane/59/07 (rg Brisbane). Convalescent sera collected from mice infected with recombinant viruses were measured for cross-reactive antibodies to pH1N1 via Hemagglutinin Inhibition (HI) or Enzyme-Linked Immunosorbent Assay (ELISA). The ectodomain of a recombinant NA protein from the pH1N1 strain (pNA-ecto) was expressed, purified and used in ELISA to measure cross-reactive antibodies. Analysis of sera from elderly humans immunized with trivalent split-inactivated influenza (TIV) seasonal vaccines prior to 2009 revealed considerable cross-reactivity to pNA-ecto. High titers of cross-reactive antibodies were detected in mice inoculated with either rg Solomon or rg Brisbane. Convalescent sera from mice inoculated with recombinant viruses were used to immunize naïve recipient Balb/c mice by passive transfer prior to challenge with pH1N1. Mice receiving rg California sera were better protected than animals receiving rg Solomon or rg Brisbane sera.ConclusionsThe NA of contemporary seasonal H1N1 influenza strains induces a cross-reactive antibody response to pH1N1 that correlates with reduced lethality from pH1N1 challenge, albeit less efficiently than anti-pH1N1 NA antibodies. These findings demonstrate that seasonal NA antibodies contribute to but are not sufficient for cross-reactive immunity to pH1N1.

Please cite this paper as: Karlsson et al. (2012) Review on the impact of pregnancy and obesity on influenza virus infection. Influenza and Other Respiratory Viruses 6(6), 449–460.A myriad of risk factors have been linked to an increase in the severity of the pandemic H1N1 2009 influenza A virus [A(H1N1)pdm09] including pregnancy and obesity where death rates can be elevated as compared to the general population. The goal of this review is to provide an overview of the influence of pregnancy and obesity on the reported cases of A(H1N1)pdm09 virus infection and of how the concurrent presence of these factors may have an exacerbating effect on infection outcome. Also, the hypothesized immunologic mechanisms that contribute to A(H1N1)pdm09 virus severity during pregnant or obese states are outlined. Identifying the mechanisms underlying the increased disease severity in these populations may result in improved therapeutic approaches and future pandemic preparedness.