Two Double‐Blinded, Randomized, Comparative Trials of 4 Human Immunodeficiency Virus Type 1 (HIV‐1) Envelope Vaccines in HIV‐1–Infected Individuals across a Spectrum of Disease Severity: AIDS Clinical Trials Groups 209 and 214

Schooley, Robert T.; Spino, Cathie; Kuritzkes, Daniel R.; Walker, Bruce D.; Valentine, Fred; Hirsch, Martin S.; Cooney, Elizabeth; Friedland, Gerald; Kundu, Smriti K.; Merigan, Thomas C.; McElrath, M. Juliana; Collier, Ann C.; Plaeger, Susan; Mitsuyasu, Ronald T.; Kahn, James S.; Haslett, Patrick; Uherova, Patricia; DeGruttola, Victor; Chiu, Simon; Zhang, Bin; Jones, Gayle; Bell, Dawn; Ketter, Nzeera; Twadell, Thomas; Chernoff, David; Rosandich, Mary

doi:10.1086/315860

Cited by 45 publications

(14 citation statements)

References 29 publications

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“…Similarly, it had been suggested from a recent study of two HIV envelope therapeutic vaccines that lymphocyte proliferative responders were more likely to have undetectable HIV RNA at baseline than non-responders, although this was not statistically significant [10].…”

Section: Discussionmentioning

confidence: 83%

Predictors of HIV-specific lymphocyte proliferative immune responses induced by therapeutic vaccination

Moss

Wallace

Steigbigel

et al. 2002

Clinical and Experimental Immunology

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SUMMARYWe treated a cohort of 38 HIV-infected individuals with a therapeutic vaccine (REMUNE, in an open label study. We then determined whether baseline parameters, such as CD4 cell count, viral load and IgG levels, were predictive of the magnitude of the HIV-specific lymphocyte proliferative responses (LPRs). We demonstrate herein that there is a significant enhancement from baseline for both HIV and p24 antigen-stimulated LPRs after immunization. Using a responder definition of a stimulation index of >5 on at least two post-immunization time-points, 29/38 (76%) responded to HIV-1 antigen while 27/38 (71%) responded to native p24 antigen. Viral load and total IgG were negatively correlated, while CD4 cell counts were positively associated with the magnitude of the HIV antigen LPR. In a multivariable analysis, baseline CD4 was the best predictor of HIV antigen LPR post-immunization.

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Section: Discussionmentioning

confidence: 83%

Predictors of HIV-specific lymphocyte proliferative immune responses induced by therapeutic vaccination

Moss

Wallace

Steigbigel

et al. 2002

Clinical and Experimental Immunology

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“…The diversity of immune responses generated by these vaccines was limited (28,30,34,42,51,57). In contrast, the vaccine regimen that we used stimulated both humoral and cellular immunity in a majority of patients.…”

Section: Vol 76 2002mentioning

confidence: 99%

Safety and Immunogenicity of ALVAC vCP1452 and Recombinant gp160 in Newly Human Immunodeficiency Virus Type 1-Infected Patients Treated with Prolonged Highly Active Antiretroviral Therapy

Jin

Ramanathan

Barsoum

et al. 2002

J Virol

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In order to boost immune responses in persons in whom highly active antiretroviral therapy (HAART) was initiated within 120 days of the onset of symptoms of newly acquired human immunodeficiency virus type 1 (HIV-1) infection, we administered vaccines containing a canarypox virus vector, vCP1452, with HIV-1 genes encoding multiple HIV-1 proteins, and recombinant gp160. Fifteen HIV-1-infected subjects who achieved sustained suppression of plasma viremia for at least 2 years were enrolled. While continuing antiretroviral therapy, each subject received at least four intramuscular injections of the vaccines on days 0, 30, 90, and 180. Adverse events were mild, with the most common being transient tenderness at the vCP1452 injection site. Of the 14 patients who completed vaccination, 13 had significant increases in anti-gp120 or anti-p24 antibody titers, and 9 had transient augmentation of their T-cell proliferation responses to gp160 and/or p24. HIV-1-specific CD8؉ T cells were quantified using an intracellular gamma interferon staining assay. Among 11 patients who had increased CD8 ؉ T-cell responses, seven had responses to more than one HIV-1 antigen. In summary, vaccination with vCP1452 and recombinant gp160 appears safe and immunogenic in newly HIV-1-infected patients on HAART.

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“…Various strategies (e.g., the use of adjuvants and multimeric and multivalent immunogens) were employed to increase vaccine immunogenicity and crossreactivity. Although these approaches proved capable of eliciting high-titered type-specific neutralizing antibodies to tissue culture lab-adapted virus strains in addition to some lymphoproliferative responses in immunized patients, these antibodies failed to neutralize primary viral isolates (49)(50)(51).…”

Section: Hiv-1 Vaccine Clinical Trialsmentioning

confidence: 99%

Progress on new vaccine strategies against chronic viral infections

Berzofsky¹,

Ahlers²,

Janik³

et al. 2004

J. Clin. Invest.

101

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Among the most cost-effective strategies for preventing viral infections, vaccines have proven effective primarily against viruses causing acute, self-limited infections. For these it has been sufficient for the vaccine to mimic the natural virus. However, viruses causing chronic infection do not elicit an immune response sufficient to clear the infection and, as a result, vaccines for these viruses must elicit more effective responses -quantitative and qualitative -than does the natural virus. Here we examine the immunologic and virologic basis for vaccines against three such viruses, HIV, hepatitis C virus, and human papillomavirus, and review progress in clinical trials to date. We also explore novel strategies for increasing the immunogenicity and efficacy of vaccines.

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Two Double‐Blinded, Randomized, Comparative Trials of 4 Human Immunodeficiency Virus Type 1 (HIV‐1) Envelope Vaccines in HIV‐1–Infected Individuals across a Spectrum of Disease Severity: AIDS Clinical Trials Groups 209 and 214

Cited by 45 publications

References 29 publications

Predictors of HIV-specific lymphocyte proliferative immune responses induced by therapeutic vaccination

Predictors of HIV-specific lymphocyte proliferative immune responses induced by therapeutic vaccination

Safety and Immunogenicity of ALVAC vCP1452 and Recombinant gp160 in Newly Human Immunodeficiency Virus Type 1-Infected Patients Treated with Prolonged Highly Active Antiretroviral Therapy

Progress on new vaccine strategies against chronic viral infections

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