Immunity to pre-1950 H1N1 influenza viruses confers cross-protection against the pandemic swine-origin 2009 A (H1N1) influenza virus.

The 2009 H1N1 influenza virus outbreak is the first pandemic of the twenty-first century. Epidemiological data reveal that of all the people afflicted with H1N1 virus, <5% are over 51 y of age. Interestingly, in the uninfected population, 33% of those >60 y old have pre-existing neutralizing Abs against the 2009 H1N1 virus. This finding suggests that influenza strains that circulated 50-60 y ago might provide cross-protection against the swine-origin 2009 H1N1 influenza virus. To test this, we determined the ability of representative H1N1 influenza viruses that circulated in the human population from 1930 to 2000, to induce cross-reactivity to and cross-protection against the pandemic swine-origin H1N1 virus, A/California/04/09. We show that exposure of mice to the 1947 virus, A/FM/1/47, or the 1934 virus, A/PR/8/34, induced robust cross-protective immune responses and these mice were protected against a lethal challenge with mouse-adapted A/California/04/09 H1N1 virus. Conversely, we observed that mice exposed to the 2009 H1N1 virus were protected against a lethal challenge with mouse-adapted 1947 or 1934 H1N1 viruses. In addition, exposure to the 2009 H1N1 virus induced broad cross-reactivity against H1N1 as well as H3N2 influenza viruses. Finally, we show that vaccination with the older H1N1 viruses, particularly A/FM/1/47, confers protective immunity against the 2009 pandemic H1N1 virus. Taken together, our data provide an explanation for the decreased susceptibility of the elderly to the 2009 H1N1 outbreak and demonstrate that vaccination with the pre-1950 influenza strains can cross-protect against the pandemic swine-origin 2009 H1N1 influenza virus.

17ß-Estradiol restores antibody responses to an influenza vaccine in a postmenopausal mouse model.

Post-menopausal women belong to an age group that is highly susceptible to influenza infection and its most serious complications. However, data on the immunogenicity of influenza vaccines in these women is limited. Therefore, the antibody response to influenza vaccination was assessed in a postmenopausal mouse model. An inactivated-detergent-split vaccine from the A/New Caledonia/20/99 (H1N1) influenza virus strain was given to three groups of mice: ovariectomized (OVEX), OVEX with 17ß-estradiol replacement (OVEX+E2), and sham-OVEX. The OVEX+E2 group produced influenza virus-specific serum antibodies, including neutralizing antibodies, at significantly higher levels (p<0.001) than did OVEX mice. These levels matched those observed in the sham-OVEX group, indicating that ovariectomy negatively modulates the antibody response to the influenza vaccine, whereas 17ß-estradiol replacement restores this response to levels observed in intact animals. Our findings suggest that immunogenicity and efficacy of influenza vaccines need to be evaluated in postmenopausal women, including women receiving hormone replacement therapy.

Sooty mangabey (Cercocebus torquatus atys) IGHG and IGHA genes.

Antibodies are adaptor molecules of the immune system that link antigen recognition with the effector mechanisms responsible for antigen clearance. Several nonhuman primate species are widely used in biomedical research, especially for vaccine development and for AIDS-related studies. However, nonhuman primate antibody molecules have been characterized only partially and only in a few species. Here, we describe sooty mangabey (Cercocebus torquatus atys) IGHG and IGHA genes, which encode the heavy-chain constant region of IgG and IgA molecules, respectively. The four mangabey IGHG genes are highly homologous to the rhesus macaque and baboon IGHG genes (percent identity varies between 94.0 and 98.8, depending on the subclass), with most amino acid differences located in the hinge regions. Results obtained by real-time reverse transcription polymerase chain reaction show that the four IGHG genes are expressed at least at the mRNA level. The mangabey IGHA gene is highly homologous to the corresponding gene from rhesus macaques (percent identity ranges from 88.6 to 96.7, depending on the allele considered), the only other nonhominoid primate species for which the complete sequence of the IGHA gene is currently available. In the mangabey analyzed, two IGHA alleles are present, confirming that high levels of IGHA gene heterozygosity are present in monkey species. These results show that nonhuman primate gamma and alpha heavy chains differ from each other mostly at the level of the hinge region and that alpha sequence heterogeneity in nonhuman primate species is also present in other gamma regions. In addition, these results provide sequence information that can be used for residue frequency analysis of antibody heavy-chain constant region sequences.