Elsevier

Vaccine

Volume 13, Issue 17, 1995, Pages 1697-1705
Vaccine

Paper
Construction and immunogenicity of Salmonella typhimurium vaccine vectors that express HIV-1 gp120

https://doi.org/10.1016/0264-410X(95)00106-BGet rights and content

Abstract

Since the human immunodeficiency virus (HIV-1) is transmitted either parenterally or sexually, both mucosal and systemic immune responses may be required to provide protective immunity. Attenuated Salmonella vectors expressing heterologous antigen can stimulate responses in both compartments. To evaluate the utility of Salmonella vectors as an HIV-1 vector vaccine, a gene expression cassette encoding recombinant HIV-1 gp120 (rgp120) was integrated into the hisOGD locus of Salmonella typhimurium aroA strain, SL3261 (SL3261::120). To test if increased antigen expression potentiates immunogenicity, strains were constructed that express rgp120 from a multicopy asd-stabilised plasmid (SL7207 pYA:120). Immunoblot analysis demonstrated that SL7207 pYA:120 expressed approximately 50-fold more rgp120 than SL3261::120. Oral immunization of BALBc mice with these strains did not stimulate an env-specific CTL response or a significant rise in antigp120 antibody titer as compared to controls. However, splenic T cells from SL7207 pYA::120 immunized mice proliferated upon restimulation with gp120 in vitro while splenocytes from SL3261::120 immunized mice did not. gp120 restimulated splenic T cells from SL7207 pYA:120 immune mice also produced IFN-γ but no IL-5. Two conclusions can be drawn from these results. First, high level expression of rgp120 in Salmonella vectors is necessary to stimulate a gp120-specific immune response in mice. Second, Salmonella::rgp120 stimulates a gp120-specific Th1 response in mice. This is the first report to describe the construction of a Salmonella::rgp120 vector vaccine that is immunogenic in mice.

References (52)

  • J.C. Sadoff et al.

    Oral Salmonella typhimurium vaccine expressing circumsporozoite protein protects against malaria

    Science

    (1988)
  • A. Aggarwal et al.

    Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells

    J. Exp. Med.

    (1990)
  • J.P. Tite et al.

    Anti-viral immunity induced by recombinant nucleoprotein of infuenza A virus: III. Delivery of recombinant nucleoprotein to the immune system using attenuated Salmonella typhimurium as a live carrier

    Immunology

    (1990)
  • H.J. Aizpurua et al.

    Oral vaccination: identi-fication of classes of proteins that provoke an immune response upon oral feeding

    J. Exp. Med.

    (1988)
  • G.B. Mackaness et al.

    Host-parasite relations in mouse typhoid

    J. Exp. Med.

    (1966)
  • R. Schindier et al.

    Culture of neoplastic mast cells and their synthesis of 5-hydroxytryptamine and histamine in vitro

    Cancer Res.

    (1959)
  • H. Takahashi et al.

    An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes

  • R.H. Schwartz

    T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex

    Ann. Rev. Immunol.

    (1985)
  • J.H. Miller

    A Short Course in Bacterial Genetics: A Laboratory Manual and Handbook for Escherichia coli and Related Bacteria

    (1992)
  • N.R. Benson et al.

    Rapid mapping in Salmonella typhimurium with Mud-P22 prophage

    J. Bacteriol.

    (1992)
  • D. Hone et al.

    Construction of genetically defined double aro mutants of Salmonella typhi

    Vaccine

    (1992)
  • J. Sambrook et al.

    Molecular Cloning: A Laboratory Manual

    (1989)
  • H. Schmieger

    Phage P22-mutants with increased or decreased transduction abilities

    Mol. Gen. Genet.

    (1972)
  • S.K. Hoiseth et al.

    Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines

    Nature (London)

    (1981)
  • Y.H. Abacioglu et al.

    Epitope mapping and topology of baculovirus-expressed HIV-1 gp160 determined with a panel of murine monoclonal antibodies

    AIDS Res. Hum. Retrovir.

    (1994)
  • J.P. Moore

    Simple methods for monitoring HIV-1 and HIV-2 gp120 binding to soluble CD4 by enzyme-linked immunosorbent assay: HIV-2 has a 25-fold lower affinity than HIV-1 for soluble CD4

    AIDS

    (1990)
  • Cited by (36)

    • Vaccines for Human Immunodeficiency Virus Type 1 Infection

      2014, Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
    • Immune response and protective efficacy of live attenuated Salmonella vaccine expressing antigens of Mycobacterium avium subsp. paratuberculosis against challenge in mice

      2012, Vaccine
      Citation Excerpt :

      Attenuated derivatives of Salmonella enterica have been used as a delivery system for heterologous antigens to induce protective immunity against several infectious diseases in model animals [12–14]. Vaccination with live attenuated Salmonella expressing various heterologous antigens (HIV Gag, gp120 and Ag85A) not only resulted in the generation of strong TH1 biased systemic immune response [15–19] but also augmented mucosal immunity [18]. However, the potential of attenuated Salmonella expressing protective MAP antigens as a vaccine candidate against MAP infection has not been evaluated to date.

    • Immunologic basis of vaccine vectors

      2010, Immunity
      Citation Excerpt :

      Several attributes of bacteria led to their development as vaccine vectors. These included the ability to deliver them via the oral route, which is the natural route of infection for a variety of bacteria such as Salmonella (Fouts et al., 1995a; Fouts et al., 1995b), (Chin'ombe et al., 2009), (Huang et al., 2009), Shigella (Fennelly et al., 1999), and certain Mycobacteria such as M. bovis (Ferrari et al., 2000). Of note, attenuated bacteria are used.

    • Salmonella vaccines for use in humans: Present and future perspectives

      2002, FEMS Microbiology Reviews
      Citation Excerpt :

      In other studies, it was found that the gp120 antigen of human immunodeficiency virus-1 formed inclusion bodies when expressed in the Salmonella cytosol, but could be produced in a soluble form when the antigen was secreted [81,119].

    View all citing articles on Scopus
    View full text