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PubMed1995

[Progress in vaccination against AIDS].

Two vaccination trials against AIDS viruses are reported. The first trial was a prophylactic vaccination carried out in the pig-tailed macaque (Macacca nemestrina) against simian immunodeficiency virus (SIV) variant PBj14. The immunogen was a Semliki forest virus (SFV) recombinant expressing SFV - PBj14 envelope protein. Vaccination did not prevent infection but protected the animals against the disease (a fulminant form of AIDS that kills the animal within 12-15 days). The second trial was a therapeutic vaccination carried out with HIV-I-infected hemophilic patients. The immunogen was a toxoïd of alpha interferons. (A toxoïd of alpha interferons is an inactivated and immunogenic preparation of alpha interferons). Vaccination induced the production of neutralizing anti alpha interferon antibody. As a result, circulating alpha interferon concentrations were drastically lowered and the clinical status of patients significantly improved.

AIDS Vaccines↗
PubMed2002

Mechanisms of protection against simian immunodeficiency virus infection.

One of the obstacles to the development of an effective AIDS vaccine has been the limited information on the mechanisms of protective immunity to HIV. In macaques, immunization with attenuated simian immunodeficiency viruses (SIV) has proved to be one of the most effective strategies to induce protection against infection or disease with pathogenic lentiviruses. Infection with attenuated SIV strains induces a broad range of SIV-specific immune responses, including relatively potent cytotoxic T lymphocyte (CTL) and antibody responses. Several studies of macaques vaccinated with attenuated SIV have demonstrated correlations between CTL responses or antibody responses and protection but more detailed studies are needed to document the relative importance of these responses in protective immunity.

AIDS Vaccines↗
PubMed2003

HIV vaccine development: lessons from the past and promise for the future.

The global HIV epidemic continues to expand, exceeding previous predictions and causing tremendous suffering. An effective vaccine represents the best hope to curtail the HIV epidemic. The past fifteen years of HIV vaccine clinical trials have not identified an ideal HIV vaccine, but have provided many valuable lessons that contribute to the current generation of promising HIV vaccine regimens. An enhanced understanding of HIV and SIV immunopathogenesis has facilitated the design of vaccination regimens that elicit specific immune responses and effector mechanisms. Intensive investigation of recombinant gp120 subunit vaccines has revealed a previously unexpected complexity in eliciting neutralizing antibodies that are active against primary isolate viruses. The importance of CD8+ CTL responses in controlling HIV and SIV viremia has led to a series of vaccine candidates that effectively induce these responses. Proof that vaccination can prevent SIV/HIV disease has now been obtained in simian models of AIDS. A number of promising HIV vaccine regimens are currently being evaluated in human trials, and the pipeline of new vaccine vectors and combination regimens appears robust. Although challenges to the development of a safe and effective global HIV vaccine remain, the outlook for HIV vaccines in the future is bright.

AIDS Vaccines↗
PubMed2005

Innate immunity in experimental SIV infection and vaccination.

Innate immunity represents the first line of defence to pathogens besides the physical barrier and seems to play a role in protection against HIV/SIV infection and disease progression. High production of beta-chemokines and CD8+ T cell anti-viral factors in naive as well as in vaccinated macaques has been associated with complete or partial protection against SIV infection indicating that genetic or environmental factors may influence their production. This innate immunity may help in generating HIV/SIV-specific responses upon the first exposure to HIV/SIV. SIV subunit vaccines given by the targeted iliac lymph node route have been shown to induce an increased production of CD8+ T cell suppressor factors and beta-chemokines. Only a few vaccine studies have focused on enhancing the innate immune response against HIV/SIV. The use of unmethylated CpG motifs, HSP and GM-CSF as adjuvants in SIV vaccines has been shown to induce production of HIV/SIV-inhibiting cytokines and beta-chemokines, which seem to be important in modulating and steering the adaptive immune responses. HSP has also been shown to induce gammadelta+ T cells, which contribute to the innate immunity. More knowledge about the interplay between the innate and adaptive immune responses is important to develop new HIV/SIV vaccine strategies.

Animals↗
PubMed2003

Innate and adaptive mucosal immunity in protection against HIV infection.

Control of the HIV pandemic requires an effective vaccine. The difficulties in developing a preventive vaccine are generally believed to be due to the rapid rate of mutation of HIV that escapes cytotoxic lymphocytes (CTL) and the problems in induction of neutralising antibodies to wild strains of HIV. These difficulties should re-orientate vaccine strategy into four somewhat neglected areas of immunisation. Innate immunity, with its rapid protective response to infection that is independent of memory and relies on an optimal mucosal adjuvant. Targeting the genital and rectal mucosa, with the associated lymph nodes, as an immune response has to be elicited directly on encountering HIV during sexual intercourse. Stimulating a broadly based adaptive immune response that enhances the memory CD4(+) and CD8(+) T cells and B cells, induces maturation of dendritic cells and results in Th1 polarised immunity. Taking advantage of "experiments of nature", by utilising host antigens, as manifested by protection against HIV infection in homozygous Delta32 CCR5 individuals and in allo-immunity.

AIDS Vaccines↗