A Phase 1 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV Type 1 Subtype C Adeno-Associated Virus Vaccine

Mehendale, Sanjay; Lunzen, Jan van; Clumeck, Nathan; Rockstroh, Jürgen K.; Vets, Eva; Johnson, Philip R.; Anklesaria, Pervin; Barin, Burc; Boaz, Mark; Kochhar, Sonali; Lehrman, Jennifer; Schmidt, Claudia; Peeters, Mathieu; Schwarze‐Zander, Carolynne; Kabeya, Kabamba; Glaunsinger, Tobias; Sahay, Seema; Thakar, Madhuri; Paranjape, Ramesh; Gilmour, Jill; Excler, Jean–Louis; Fast, Patricia E.; Heald, Alison E.

doi:10.1089/aid.2007.0292

Cited by 42 publications

(36 citation statements)

References 23 publications

(34 reference statements)

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“…The vaccine was shown to be generally safe, well tolerated, and modestly immunogenic after one intramuscular injection at dosages up to 3Â10 11 DNase-resistant particles (DRP). 6 The strong T cell and antibody-mediated immune responses observed in macaques were not reproduced in this clinical study, perhaps because the dosages administered in macaques were higher, ranging from 5 to 10Â10…”

Section: Introductionmentioning

confidence: 79%

“…6 The HIV gag-pro-DRT nucleic acid is a synthetic cDNA for HIV-1 gag-protease. This includes the gag and protease coding regions and an additional 306 nucleotides of the HIV genome beyond the protease sequence, followed by a stop codon.…”

Section: Study Vaccinementioning

confidence: 99%

“…The presence of the tgAAC09 vaccine particle was determined by an infectivity assay with a PCR readout. 6 Briefly, the in vitro assay involved incubating the above-mentioned samples with C37 cells containing AAV2 rep and cap sequences in the presence of adenovirus. If tgAAC09 particles were present in the samples, the particles would enter the cells and vaccine DNA in this artificial system would be amplified.…”

Section: Study Proceduresmentioning

confidence: 99%

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A Phase 2 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV Type 1 Vaccine Based on Adeno-Associated Virus

Vardas

Kaleebu²,

Bekker³

et al. 2010

AIDS Research and Human Retroviruses

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The recombinant vaccine, tgAAC09, based on an adeno-associated virus serotype 2 (AAV2) vector encoding HIV-1 subtype C Gag, protease, and part of reverse transcriptase, induced robust T cell and antibody responses in nonhuman primates. In a previous phase I study in 80 healthy HIV-seronegative European and Indian adults, the vaccine was generally safe, well tolerated, and modestly immunogenic when administered once at doses up to 3Â10 11 DRP. This phase II double-blind, randomized, placebo-controlled trial tested two administrations and a higher dosage of tgAAC009. Ninety-one healthy HIV-seronegative adults from three African countries were given one of three dosage levels of tgAAC09 (3Â10 10 , 3Â10 11 , or 3Â10 12 DRP) intramuscularly, either at a 6-or 12-month interval; follow-up was 18 months. Overall, 65% and 57% of vaccine recipients experienced local and systemic signs and symptoms, respectively, most being mild. Frequency and severity were not dose related and were similar to those in placebo recipients. No vaccine-related serious adverse events were reported. Overall, HIV-specific T cell responses were detected by IFN-g ELISPOT in 17/69 (25%) vaccine recipients with 38% (10/26) responders in the highest dosage group. The response rate improved significantly with boosting at 6, but not 12 months, in the 3Â10 11 and 3Â10 12 dosage groups only. Neutralizing antibody titers to the AAV2 did not alter the frequency of immune responses to HIV. Two doses of tgAAC09 were well tolerated at the dosage levels given. Fewer than half the recipients of the highest vaccine dosage, 3Â10 12 DRP, had T cell responses to HIV.

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Section: Introductionmentioning

confidence: 79%

Section: Study Vaccinementioning

confidence: 99%

Section: Study Proceduresmentioning

confidence: 99%

See 1 more Smart Citation

A Phase 2 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV Type 1 Vaccine Based on Adeno-Associated Virus

Vardas

Kaleebu²,

Bekker³

et al. 2010

AIDS Research and Human Retroviruses

Self Cite

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“…[134][135][136][137] HIV vaccine clinical development came to a halt and shifted to designing immunogens able to induce HIV-specific broadly neutralizing antibodies (www.iavi.org). The prioritization of trialrelated financial and healthcare provisions, including access to an efficacious vaccine posttrial, among MSM in India indicates the importance of trials providing such services, as well as the value of formative research in identifying key concerns among participating communities in resourcelimited settings.…”

Section: Hiv Vaccine Clinical Developmentmentioning

confidence: 99%

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

Phanuphak

Shao³

et al. 2015

AIDS Research and Human Retroviruses

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An overall decrease of HIV prevalence is now observed in several key Asian countries due to effective prevention programs. The decrease in HIV prevalence and incidence may further improve with the scale-up of combination prevention interventions. The implementation of future prevention trials then faces important challenges. The opportunity to identify heterosexual populations at high risk such as female sex workers may rapidly wane. With unabating HIV epidemics among men who have sex with men (MSM) and transgender (TG) populations, an effective vaccine would likely be the only option to turn the epidemic. It is more likely that efficacy trials will occur among MSM and TG because their higher HIV incidence permits smaller and less costly trials. The constantly evolving patterns of HIV-1 diversity in the region suggest close monitoring of the molecular HIV epidemic in potential target populations for HIV vaccine efficacy trials. CRF01_AE remains predominant in southeast Asian countries and MSM populations in China. This relatively steady pattern is conducive to regional efficacy trials, and as efficacy warrants, to regional licensure. While vaccines inducing nonneutralizing antibodies have promise against HIV acquisition, vaccines designed to induce broadly neutralizing antibodies and cell-mediated immune responses of greater breadth and depth in the mucosal compartments should be considered for testing in MSM and TG. The rationale and design of efficacy trials of combination prevention modalities such as HIV vaccine and preexposure prophylaxis (PrEP) remain hypothetical, require high adherence to PrEP, are more costly, and present new regulatory challenges. The prioritization of prevention interventions should be driven by the HIV epidemic and decided by the country-specific health and regulatory authorities. Modeling the impact and cost-benefit may help this decision process.

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“…The first Indian vaccine trial conducted at NARI Pune in 2005 was a dose escalation Phase I study using the Adeno-Associated Virus recombinant vaccine (tgAAC09) (Fig. 5) which expressed HIV-1 subtype C gag protease and RT genes; was found to be safe in humans but did not generate adequate immune response [78].…”

Section: Hiv Vaccine Researchmentioning

confidence: 99%

Current Status of Research on HIV Epidemic, Pathogenesis, Management and Prevention in India

Paranjape

Thakar

Ghate

et al. 2012

Proc. Natl. Acad. Sci. Sect B. Biol. Sci.

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A Phase 1 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV Type 1 Subtype C Adeno-Associated Virus Vaccine

Cited by 42 publications

References 23 publications

A Phase 2 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV Type 1 Vaccine Based on Adeno-Associated Virus

A Phase 2 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV Type 1 Vaccine Based on Adeno-Associated Virus

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

Current Status of Research on HIV Epidemic, Pathogenesis, Management and Prevention in India

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