Search

Perfluoroalkyl substances (PFAS) were shown to be immunotoxic in laboratory animals. There is some epidemiological evidence that PFAS exposure is inversely associated with vaccine-induced antibody concentration. We examined immune response to vaccination with FluMist intranasal live attenuated influenza vaccine in relation to four PFAS (perfluorooctanoate, perfluorononanoate, perfluorooctane sulfonate, perfluorohexane sulfonate) serum concentrations among 78 healthy adults vaccinated during the 2010-2011 influenza season. We measured anti-A H1N1 antibody response and cytokine and chemokine concentrations in serum pre-vaccination, 3 days post-vaccination, and 30 days post-vaccination. We measured cytokine, chemokine, and mucosal IgA concentration in nasal secretions 3 days post-vaccination and 30 days post-vaccination. Adults with higher PFAS concentrations were more likely to seroconvert after FluMist vaccination as compared to adults with lower PFAS concentrations. The associations, however, were imprecise and few participants seroconverted as measured either by hemagglutination inhibition (9%) or immunohistochemical staining (25%). We observed no readily discernable or consistent pattern between PFAS concentration and baseline cytokine, chemokine, or mucosal IgA concentration, or between PFAS concentration and change in these immune markers between baseline and FluMist-response states. The results of this study do not support a reduced immune response to FluMist vaccination among healthy adults in relation to serum PFAS concentration. Given the study's many limitations, however, it does not rule out impaired vaccine response to other vaccines or vaccine components in either children or adults., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Influenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established., Methods: Seventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses., Results: Only 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination., Conclusions: Protection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.

Objective: To estimate the effects of gestational age and other maternal factors on immunologic responses to influenza vaccination., Methods: Antepartum and postpartum women receiving influenza vaccination as part of routine clinical care were enrolled through four consecutive vaccination seasons (starting October 2006 through January 2010). Immunologic responses to trivalent inactivated influenza vaccine and monovalent H1N1 were assessed as well as factors influencing vaccine responsiveness. Serum samples were obtained at baseline and 4-8 weeks postvaccination., Results: Two hundred thirty-nine participants were included in the current analysis. Seroconversion rates to trivalent inactivated influenza vaccine strains were lowest in the first trimester (54.8%) and immediately postpartum (54.8%) and were highest in the late third trimester (69.6%) and late postpartum (69.4%); these differences were not statistically significant (P=.23). In a multivariable model, higher baseline antibody levels (P<.001) and prior year flu vaccination (P=.03) were both significantly associated with reduced odds of seroconversion. Overall, results were consistent when comparing trivalent inactivated influenza vaccine and monovalent pandemic H1N1 responses. Although there was overall no significant association between gestational age at vaccination (P=.23) or prepregnancy body mass index (P=.16), we observed somewhat lower rates of seroconversion for women vaccinated in the first trimester and for obese women., Conclusion: Adequate immunologic responses to inactivated influenza vaccines were demonstrated during pregnancy and the postpartum period. No diminution of immunogenicity was observed in the third trimester, a time of increased clinical vulnerability to influenza.

Current influenza virus vaccines protect mostly against homologous virus strains; thus, regular immunization with updated vaccine formulations is necessary to guard against the virus' hallmark remodeling of regions that mediate neutralization. Development of a broadly protective influenza vaccine would mark a significant advance in human infectious diseases research. Antibodies with broad neutralizing activity (nAbs) against multiple influenza virus strains or subtypes have been reported to bind the stalk of the viral hemagglutinin, suggesting that a vaccine based on this region could elicit a broadly protective immune response. Here we describe a hemagglutinin subunit 2 protein (HA2)-based synthetic peptide vaccine that provides protection in mice against influenza viruses of the structurally divergent subtypes H3N2, H1N1, and H5N1. The immunogen is based on the binding site of the recently described nAb 12D1, which neutralizes H3 subtype viruses, demonstrates protective activity in vivo, and, in contrast to a majority of described nAbs, appears to bind to residues within a single α-helical portion of the HA2 protein. Our data further demonstrate that the specific design of our immunogen is integral in the induction of broadly active anti-hemagglutinin antibodies. These results provide proof of concept for an HA2-based influenza vaccine that could diminish the threat of pandemic influenza disease and generally reduce the significance of influenza viruses as human pathogens.

There is a substantial need to develop better influenza virus vaccines that can protect populations that are not adequately protected by the currently licensed vaccines. While live attenuated influenza virus vaccines induce superior immune responses compared to inactivated vaccines, the manufacturing process of both types of influenza virus vaccines is time consuming and may not be adequate during a pandemic. Adjuvants would be particularly useful if they could enhance the immune response to live attenuated influenza virus vaccines so that the amount of vaccine needed for a protective dose could be reduced. The glycolipid, alpha-galactosylceramide (alpha-GalCer), has recently been shown to have adjuvant activity for both inactivated and replicating recombinant vaccines. The goal of these experiments was to determine whether a derivative of alpha-GalCer, alpha-C-galactosylceramide (alpha-C-GalCer) can enhance the immune response elicited by a live attenuated influenza virus vaccine containing an NS1 protein truncation and reduce the amount of vaccine required to provide protection after challenge. Our results indicated that the adjuvant reduced both morbidity and mortality in BALB/c mice after challenge with wild type influenza virus. The adjuvant also increased the amount of influenza virus specific total IgG, IgG1, and IgG2a antibodies as well as IFN-gamma secreting CD8(+) T cells. By using knockout mice that are not able to generate NKT cells, we were able to demonstrate that the mechanism of adjuvant activity is dependent on NKT cells. Thus, our data indicate that stimulators of NKT cells represent a new avenue of adjuvants to pursue for live attenuated virus vaccines.

Background: Annual influenza vaccination is routinely recommended for pediatric solid organ transplant recipients. However, there are limited data defining the immune response to the inactivated vaccine in this population., Methods: This prospective study compared the humoral and cell-mediated immune responses to the trivalent subvirion influenza vaccine in pediatric liver transplant recipients with those in their healthy siblings. All subjects received inactivated influenza vaccine. Hemagglutination inhibition and interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays for New Caledonia and Shanghai strains were performed at baseline, after each vaccine dose, and 3 months after the series. Seroconversion was defined as a 4-fold increase in antibody titers; seroprotection was defined as an antibody titer > or =1:40. An increase in the number of T cells secreting IFN-gamma was considered to be a positive enzyme-linked immunosorbent spot response., Results: After 1 dose of vaccine, transplant recipients achieved rates of antibody seroprotection and seroconversion that were similar to those achieved by their healthy siblings. However, for both influenza strains, IFN-gamma responses by enzyme-linked immunosorbent spot were significantly attenuated in transplant recipients after 2 doses of vaccine. No cases of influenza or vaccine-related serious adverse events were documented in the study., Conclusions: The diminished cell-mediated immune response to influenza vaccination that was observed in pediatric liver transplant recipients suggests that the current vaccine strategy may not provide optimal protection. Because of concerns regarding potential emergence of more virulent influenza strains, further studies are warranted to determine if IFN-gamma responses are predictive of efficacy and to identify the optimal vaccination strategy to protect populations with a high risk of infection.