Preexisting poliovirus-specific IgA in the circulation correlates with protection against virus excretion in the elderly

Center for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
The Journal of Infectious Diseases (Impact Factor: 5.78). 04/2008; 197(5):698-706. DOI: 10.1086/527487
Source: PubMed

ABSTRACT Epidemiological studies have indicated that at least 10% of the Dutch elderly do not have poliovirus serotype-specific neutralizing antibody titers and might be at risk for poliovirus infection. Previously we established that memory immunity does not protect the elderly against poliovirus replication. In this study, we investigated whether preexisting immunoglobulin (Ig) A protects against poliovirus infection.
Elderly individuals (n = 383), divided into seronegative and seropositive groups, were challenged with monovalent oral poliovirus vaccine (mOPV), either serotype 1 or serotype 3. After challenge, poliovirus serotype-specific circulating and salivary IgA responses were measured by enzyme-linked immunosorbent assays, and poliovirus excretion in stool was measured.
The majority of elderly persons without preexisting IgA excreted poliovirus in the stool. In contrast, most elderly persons seropositive for IgA did not excrete poliovirus. Significant inverse correlations were found between preexisting titers of poliovirus serotype-specific circulating IgA and virus excretion. Challenge with mOPV (re)induced IgA responses; low salivary IgA responses correlated with that in the circulation but not with virus excretion.
These results indicate that preexisting IgA values in the circulation correlate with protection against poliovirus infection in the elderly. This further implies that persons without preexisting IgA might contribute to the circulation of poliovirus and therefore may threaten its eradication.


Available from: Tineke Herremans, Jun 11, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: An estimated 90% of all HIV transmissions occur mucosally. Immunoglobulin A (IgA) molecules are important components of mucosal fluids. In a vaccine efficacy study, in which virosomes displaying HIV gp41 antigens protected most rhesus monkeys (RMs) against simian-human immunodeficiency virus (SHIV), protection correlated with vaginal IgA capable of blocking HIV transcytosis in vitro. Furthermore, vaginal IgG exhibiting virus neutralization and/or antibody-dependent cellular cytotoxicity (ADCC) correlated with prevention of systemic infection. In contrast, plasma IgG had neither neutralizing nor ADCC activity. More recently, a passive mucosal immunization study provided the first direct proof that dimeric IgAs (dIgAs) can prevent SHIV acquisition in RMs challenged mucosally. This study compared dimeric IgA1 (dIgA1), dIgA2, or IgG1 versions of a human neutralizing monoclonal antibody (nmAb) targeting a conserved HIV Env epitope. While the nmAb neutralization profiles were identical in vitro, dIgA1 was significantly more protective in vivo than dIgA2. Protection was linked to a new mechanism: virion capture. Protection also correlated with inhibition of transcytosis of cell-free virus in vitro. While both of these primate model studies demonstrated protective effects of mucosal IgAs, the RV144 clinical trial identified plasma IgA responses to HIV Env as risk factors for increased HIV acquisition. In a secondary analysis of RV144, plasma IgA decreased the in vitro ADCC activity of vaccine-induced, Env-specific IgG with the same epitope specificity. Here we review the current literature regarding the potential of IgA ¿ systemic as well as mucosal ¿ in modulating virus acquisition and address the question whether anti-HIV IgA responses could help or harm the host.
    Retrovirology 12/2014; 11(1):109. DOI:10.1186/PREACCEPT-1729873135143527 · 4.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of new low cost inactivated polio virus based vaccines (IPV) is a high priority, and will be required to eradicate polio. In addition, such a vaccine constitutes the only realistic polio vaccine in the post-eradication era. One way to reduce the cost of a vaccine is to increase immunogenicity by use of adjuvants. The CAF01 adjuvant has previously been shown to be a safe and potent adjuvant with several antigens, and here we show that in mice IPV formulated with CAF01 induced increased systemic protective immunity measured by binding and neutralization antibody titers in serum. CAF01 also influenced the kinetics of both the cellular and humoral response against IPV to produce a faster, as well as a stronger, response, dominated by IgG2a, IgG2b, and IgG2c isotypes as well as IPV specific T cells secreting IFN-γ/IL-2. Finally, as intestinal immunity is also a priority of polio vaccines, we present a vaccine strategy based on simultaneous priming at an intradermal and an intramuscular site that generate intestinal immune responses against polio virus. Taken together, the IPV-CAF01 formulation constitutes a new promising vaccine against polio with the ability to generate strong humoral and cellular immunity against the polio virus.
    PLoS ONE 06/2014; 9(6):e100879. DOI:10.1371/journal.pone.0100879 · 3.53 Impact Factor
  • The Lancet 03/2014; 383(9922):1037-8. DOI:10.1016/S0140-6736(14)60514-6 · 39.21 Impact Factor