The common mucosal immune system for the reproductive tract: basic principles applied toward an AIDS vaccine

Hiroshi Kiyono, Chris J Miller, Yichen Lu, Thomas Lehner, Martin Cranage, Yung T. Huang, Shigetada Kawabata, Marta Marthas, Bryan Roberts, John G. Nedrud, Michael E. Lamm, Lesley Bergmeier, Roger Brookes, Louisa Tao, Jerry R. McGhee

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The concept of the Collaborative Mucosal Immunization Research Group for AIDS (CMIG) was originally conceived by the AIDS Vaccine Branch, National Institute of Allergy and Infectious Diseases (NIAID) in order to provide support for a cooperative research environment for the development of mucosal immunity to AIDS. We have purposely organized five groups of investigators at five different locations to determine how effective mucosal immunity to AIDS can be optimally approached. CMIG recognizes that both rectal (homosexual) as well as vaginal (heterosexual) infections with HIV are two of the major ways that AIDS currently disseminates through the human population. Thus, we have chosen the SIV model of infection of rhesus macaques, but more importantly the CMIG have joined two of our five components in order to use the significant expertise developed for mucosal transmission of SIV and immunity. Thus, we have brought the extensive expertise with vaginal and rectal immunization and immunity to spread [Drs. Chris Miller and Marta Marthas, California Regional Primate Research Center (CRPRC), Davis and Drs. Thomas Lehner and Martin Cranage, United Medical and Dental School Guy's Hospital, London and the Centre for Applied Microbiology and Research (Guy's/CAMR)]. Two additional components were added in order to perform mucosal immune response studies required to develop and to optimize a mucosal vaccine. First, extensive CD4+ T helper (Th) cell (e.g., Th1 and Th2) and CD8+ T cell subset studies are a major effort of the coordinating group at the University of Alabama at Birmingham (Drs. Hiroshi Kiyono and Jerry R. McGhee). This component is closely interacting with both the CRPRC and Guy's/CAMR components in terms of SIV-specific CD4+ and CD8+ T cell subset responses. For example, SIV-specific CTL responses are jointly examined using different techniques by CRPRC, Guy's/CAMR and UAB investigators. Further, it is also important to examine a balance between SIV-specific and Th1 and Th2 cell responses following mucosal immunization since the Th cell-derived cytokines are essential for the induction of appropriate antigen-specific mucosal immune responses. This issue is currently being extensively examined by the CMIG effort and a summary of our findings is discussed in this review. A major question in mucosal immunity involves the functions of secretory IgA (S-IgA) antibodies and this area is of particular importance in rectal and reproductive tract immunity. A novel and exciting in vitro epithelial cell assay system is used to study how effectively S-IgA neutralizes SIV infection (Drs. John Huang, John Nedrud and Michael Lamm, Case Western Reserve, Cleveland). A clear advantage of this CMIG effort is the unique expertise in design of mucosal delivery systems for an AIDS vaccine. We are using state-of-the-art recombinant bacteria, i.e.. rSalmonella and rVibrios for mucosal immunization [Drs. Yichen Lu and Bryan Roberts, Virus Research Institute (VRI), Boston]. In addition, we are also testing other mucosal delivery systems including DNA vaccine, microspheres, cholera toxin (CT) and CT-B, recombinant poliovirus, and immune complexes. These studies represent the first efforts to induce not only Th cell mediated S-IgA responses, but also CTL responses to SIV in primates immunized with different mucosal vector delivery systems. In order to focus our effort for the induction of SIV-specific immune responses following mucosal immunization, investigators from the CMIG are attempting to understand the induction and regulation of antigen-specific immune responses in rhesus macaques mucosally immunized with different preparations of SIV vaccines.

Original languageEnglish (US)
Pages (from-to)23-52
Number of pages30
JournalAdvanced Drug Delivery Reviews
Volume18
Issue number1
DOIs
StatePublished - Dec 15 1995

Keywords

  • DNA vaccine
  • HIV-1 non-replicative viron
  • Mucosal AIDS
  • Mucosal immunity
  • Mucosal vaccine
  • Polyphosphazene microencapsulation
  • S. typhi vector
  • Th1 cell
  • Th2 cell
  • V. Cholera vector

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Kiyono, H., Miller, C. J., Lu, Y., Lehner, T., Cranage, M., Huang, Y. T., Kawabata, S., Marthas, M., Roberts, B., Nedrud, J. G., Lamm, M. E., Bergmeier, L., Brookes, R., Tao, L., & McGhee, J. R. (1995). The common mucosal immune system for the reproductive tract: basic principles applied toward an AIDS vaccine. Advanced Drug Delivery Reviews, 18(1), 23-52. https://doi.org/10.1016/0169-409X(95)00049-D