Exclusion of HIV epitopes shared with human proteins is prerequisite for designing safer AIDS vaccines

Maksyutov, A. Z.; Bachinskii, A. G.; Bazhan, Sergei I.; Ryzhikov, Evgenii А.; Maksyutov, Zaki A.

doi:10.1016/j.jcv.2004.09.007

Cited by 23 publications

(14 citation statements)

References 27 publications

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“…This would either be due to homologies in the gp41 MPER with self antigens [127], self recognition of the lipid components of the viral membrane [106], or cross-reactivity of the MPER with, as yet unknown environmental or commensural bacterial antigens. If tolerance proves to be a factor in limiting anti-MPER antibody production, antibodies made in the setting of breaks in tolerance could be expected to have some degree of polyspecificity for self antigens.…”

Section: Antibody Escape and Evasion Mechanisms Of Hiv-1mentioning

confidence: 99%

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Haynes¹,

Montefiori²

2006

Expert Review of Vaccines

103

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Neutralizing antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and complex immune-evasion strategies of HIV-1 have thwarted all attempts to date at eliciting an effective neutralizing antibody response with candidate HIV-1 vaccine immunogens. Recent advances in our understanding of how these evasion strategies operate, coupled with growing progress in unravelling the structure and immunobiology of the viral envelope glycoproteins, are contributing to novel immunogen designs to overcome the many barriers to inducing protective antibodies against HIV-1. Keywordsantiretroviral therapy; HIV-1; host cell fusion; immunogen; neutralizing antibody induction Development of a safe, practical and effective HIV-1 vaccine is one of the highest priorities of the global scientific community [1,2]. Although antiretroviral therapy (ART) has dramatically prolonged the lives of HIV-1 infected patients, ART is not yet routinely available in developing countries, and the global rate of spread of HIV-1 continues unabated. If no effective AIDS vaccine is developed by 2010, the number of people infected world-wide with HIV-1 could exceed 60 million [3].In spite of more than 20 years of research, the types of immune responses needed to protect an immunized individual from HIV-1 infection are not known. Its is known that CD8 + cytotoxic T-cell responses can control HIV-1 replication to varying degrees in acute HIV-1 infection (AHI) [4,5], and when induced by immunogens, can control viral set point after simian immunodeficiancy virus (SIV) or simian HIV (SHIV) challenges in non-human primates [4]. Strong proliferative CD4 + T-cell responses to HIV-1 proteins have been demonstrated to correlate well with immune control of HIV-1 viral load [5]. Therefore, it is highly desirable for an HIV-1 vaccine co induce robust CD4 + and CD8 + T-cell responses in order to control virus replication and reduce the likelihood of subsequent transmission [4][5][6][7]. The potential for complete ('sterilizing') immunity from HIV-1 infection may depend on the presence of pre-existing neutralizing antibodies. We know that neutralizing antibodies can prevent the acquisition of AIDS virus infection after intravenous, vaginal, rectal and oral virus challenge in nonhuman primates [8][9][10][11][12]. This level of protection is highly attractive for a vaccine against a virus, such as HIV-1, which integrates genetically and forms latent viral reservoirs soon after infection. However, the diversity of transmitted HIV-1 genetic variants and the relative resistance of the majority of HIV-1 primary isolates to most types of inducible neutralizing antibodies have posed major hurdles to current vaccine efforts. Furthermore, the few rare broadly reactive neutralizing monoclonal antibodies (mAbs) that have been isolated from HIV-1 infected patients represent species of antibodies that...

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Section: Antibody Escape and Evasion Mechanisms Of Hiv-1mentioning

confidence: 99%

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Haynes¹,

Montefiori²

2006

Expert Review of Vaccines

103

View full text Add to dashboard Cite

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“…The local similarity of fragments of viral proteins from the candidate peptide vaccine with normal human proteins was analyzed by the formerly developed methodology by Maksyutov et al (2004) for searching locally similar fragments in proteins of both the TBE virus and humans. The E protein sequence of TBE virus, strain Sofjin, was extracted from SWISS- PROT (rl.…”

Section: Theoretical Analysismentioning

confidence: 99%

Intranasal immunization with inactivated tick-borne encephalitis virus and the antigenic peptide 89–119 protects mice against intraperitoneal challenge

Гончарова

Ryzhikov

Poryvaev

et al. 2006

International Journal of Medical Microbiology

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“…This adds another layer of complexity since HIV proteins appear to be more "human" than we thought. Furthermore, Root-Bernstein found out that HIV also shares antigenic determinants with opportunistic pathogens commonly found in AIDS patients [139]. These cofactor infections elicited complementary (idiotype-antiidiotype) antibodies and some of these antibodies also mimicked host lymphocyte-directed antibodies.…”

Section: Autoimmune and Alloimmune Aspects Of Hiv Diseasementioning

confidence: 98%

Therapeutic AIDS Vaccines

Bourinbaiar¹,

Root‐Bernstein²,

Abulafia-Lapid³

et al. 2006

CPD

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Therapeutic HIV vaccines represent promising strategy as an adjunct or alternative to current antiretroviral treatment options for HIV. Unlike prophylactic AIDS vaccines designed to prevent HIV infection, therapeutic vaccines are given to already infected individuals to help fight the disease by modulating their immune response. The first immunotherapeutic trial in AIDS patients was conducted in 1983. Since then several dozen conventional therapeutic vaccine trials have been carried out. Unfortunately, the results have consistently shown that while HIV-specific immune responses were evident as a result of vaccination, the clinical improvement has been seldom observed. The instances of the apparent clinical benefit were invariably associated with unconventional vaccines that acted in accord with the principles of alloimmunization and/or autologous vaccination. All such vaccines were derived from the blood of HIV carriers or a cell culture and thus they inherently contained allo- or self-antigens unrelated to HIV. This intriguing observation raises the issue whether this clinically successful approach has been unduly neglected. The current strategy biased toward vaccines, which have shown little evidence of clinical efficacy, needs to be diversified and supplemented with research on alternative vaccine approaches geared toward immune tolerance induction.

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Exclusion of HIV epitopes shared with human proteins is prerequisite for designing safer AIDS vaccines

Cited by 23 publications

References 27 publications

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Intranasal immunization with inactivated tick-borne encephalitis virus and the antigenic peptide 89–119 protects mice against intraperitoneal challenge

Therapeutic AIDS Vaccines

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