In Thailand, phase 1/2 trials of monovalent subtype B and bivalent subtype B/E (CRF01_AE) recombinant glycoprotein 120 human immunodeficiency virus type 1 (HIV-1) vaccines were successfully conducted from 1995 to 1998, prompting the first HIV-1 vaccine efficacy trial in Asia.
This randomized, double-blind, placebo-controlled efficacy trial of AIDSVAX B/E (VaxGen), which included 36-months of follow-up, was conducted among injection drug users (IDUs) in Bangkok, Thailand. The primary end point was HIV-1 infection; secondary end points included plasma HIV-1 load, CD4 cell count, onset of acquired immunodeficiency syndrome-defining conditions, and initiation of antiretroviral therapy.
A total of 2546 IDUs were enrolled between March 1999 and August 2000; the median age was 26 years, and 93.4% were men. The overall HIV-1 incidence was 3.4 infections/100 person-years (95% confidence interval [CI], 3.0-3.9 infections/100 person-years), and the cumulative incidence was 8.4%. There were no differences between the vaccine and placebo arms. HIV-1 subtype E (83 vaccine and 81 placebo recipients) accounted for 77% of infections. Vaccine efficacy was estimated at 0.1% (95% CI, -30.8% to 23.8%; P=.99, log-rank test). No statistically significant effects of the vaccine on secondary end points were observed.
Despite the successful completion of this efficacy trial, the vaccine did not prevent HIV-1 infection or delay HIV-1 disease progression.
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"Two failed phase III HIV-1 vaccine trials using recombinant gp120 proteins (AIDSVAX)414243 led to the conclusion in the HIV vaccine field that a monomeric gp120 immunogen may not be effective in eliciting protective immune responses. Designing more effective HIV-1 Env immunogens is a major challenge for the development of next generation HIV-1 vaccines. "
[Show abstract][Hide abstract] ABSTRACT: DNA vaccination has been studied in the last 20 years for HIV vaccine research. Significant experience has been accumulated in vector design, antigen optimization, delivery approaches and the use of DNA immunization as part of a prime-boost HIV vaccination strategy. Key historical data and future outlook are presented. With better understanding on the potential of DNA immunization and recent progress in HIV vaccine research, it is anticipated that DNA immunization will play a more significant role in the future of HIV vaccine development.
"The vaccine was changed to AIDSVAX B/E to reflect common virus subgroups as former one (Pitisuttithum et al., 2006). Again, the results of the study showed that the vaccine did not prevent HIV infection nor did it delay disease progression (Pitisuttithum et al., 2006). Given the slow progress in developing effective vaccines using traditional approaches, novel vaccine technologies, which include plasmid DNA vaccines and live recombinant vectors, are also being investigated (Barouch, 2008). "
[Show description][Hide description] DESCRIPTION: Human immunodeficiency virus (HIV) has one of the highest incidence and mortality rates of any
infectious disease, with more than 33 million people infected worldwide. Specifically, HIV causes the
destruction of helper T cells, ultimately resulting in the suppression of the immune system and leaving
its human host susceptible to countless of other pathogenic agents. The development of an effective
HIV vaccine has continued for more than 20 years. But the use of preventative vaccines using traditional
vaccine technologies, which have proven successful for other diseases, has thus far failed with HIV.
One vaccine, AIDSVAX, was the first HIV vaccine to reach a phase III efficacy trial, but has not yet been
shown to eradicate HIV. Hope now lies in the development of therapeutic vaccines using novel
technologies. One such vaccine is ALVAC-HIV, which when used in conjunction with other vaccines
(AIDSVAX or Lipo-6T with IL-2 injections) has shown a great deal of promise in clinical trials
suppressing viral replication and improving the immune system. Other therapeutic vaccines, such as
Ad5, however, have been unsuccessful. While many believed that developing an effective HIV vaccine is
impossible, efforts continue into researching its structure, transmission, immune system suppression,
genetic variability, and immune system evasion. As long as research continues, hope remains that
someday an effective vaccine will be developed.
"It is widely accepted that an effective prophylactic vaccine against HIV-1 should elicit neutralizing antibodies (Nabs) that, if present at the time of transmission, could block HIV acquisition. However, all vaccine candidates based on the induction of neutralizing antibodies failed to induce Nabs and also failed large-scale efficacy phase III trials  . Therefore, the HIV prophylactic vaccine research shifted to evaluate vaccine candidates capable of inducing cell-mediated immune responses (CMI). "
[Show abstract][Hide abstract] ABSTRACT: The development of an effective HIV vaccine is still a major scientific challenge. HIV vaccine trials conducted until now were not able to induce broad neutralizing antibodies or effective cell mediated immune responses. More recently, CD4+ T cells have been shown to play an important role in viral control and better disease prognosis. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4+ T cell responses in BALB/c and in multiple HLA class II transgenic mice. Despite the advantages of DNA vaccines and a large number of clinical trials, it has been a challenge to transfer the success of inducing potent immunity observed in animal models to humans. Here, we sought to evaluate the potential use of bupivacaine, a local anesthetic, as an adjuvant for HIVBr18. We observed that the concomitant administration of the local anesthetic bupivacaine with the DNA vaccine HIVBr18 increased the magnitude of CD4+ and CD8+ T cell responses and cytokine production without compromising their breadth. Furthermore, we demonstrate that coadministration of bupivacaine also impacted the longevity of specific immune responses. Since bupivacaine is used in clinical settings, we believe that this concept may contribute to overcome the limited immunogenicity of DNA vaccines in humans.
Full-text · Article · Dec 2014 · Trials in Vaccinology