Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial

Pitisuttithum, Punnee; Nitayaphan, Sorachai; Chariyalertsak, Suwat; Kaewkungwal, Jaranit; Dawson, Peter; Dhitavat, Jittima; Phonrat, Benjaluck; Akapirat, Siriwat; Karasavvas, Nicos; Wieczorek, Lindsay; Polonis, Victoria R.; Eller, Michael A.; Pegu, Poonam; Kim, Do-Hoon; Schuetz, Alexandra; Jongrakthaitae, Surat; Zhou, Yingjun; Sinangil, Faruk; Phogat, Sanjay; DiazGranados, Carlos A.; Tartaglia, James; Heger, Elizabeth; Smith, Kirsten; Michael, Nelson L.; Excler, Jean Louis; Robb, Merlin L.; Kim, Jerome H.; O’Connell, Robert J.; Vasan, Sandhya; Pitisuthitham, Arom; Sabmee, Yupa; Sirisopana, Narongrid; Eamsila, Chirapa; Savaraj, Prapaporn; Labwech, Wanlaya; Teerachia, Siriluck; Chotirosniramit, Nuntisa; Supindham, Taweewat; Pruenglampoo, Boonlure; Sugandhavesa, Patcharaphan; Kosashunhanan, Natthapol; Kaewthip, Oranitcha; Sroysuwan, Piyathida; Jarujareet, Pawinee; Ratto‐Kim, Silvia; Molnar, Sebastian; Schoen, Jesse; Churikanont, Nampueng; Getchalarat, Saowanit; Sangnoi, Nongluck; Nuntapinit, Bessara; Phramtong, Anant; Grandin, Pornsuk V.; Madnote, Sirinan; Rittiroongrad, Surawach; Kaewboon, Boot; Trichavaroj, Rapee; Puangkaew, Jiraporn; Chantakulkij, Somsak; Rakyat, Phiromrat; Panjapornsuk, Pornchanok; Tragonlugsana, Nipattra; Chuenarom, Weerawan; Souza, Mark de; Ngauy, Viseth; Phanuphak, Nittaya; Chomchey, Nitiya; Saengtawan, Puttachard; Teeratakulpisarn, Nipat; Rerknimitr, Rungsun; Kroon, Eugène; Lee, Carter A.; Chinaworapong, Suchada

doi:10.1016/s2352-3018(19)30406-0

Cited by 37 publications

(35 citation statements)

References 29 publications

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“…The prime–boost interval in a vaccination schedule may, in turn, significantly influence both the short- and long-term immune response to the vaccination and is often very challenging to determine. This aspect has been studied in some pre-clinical [ 25 , 26 ] and clinical studies [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. During the actual SARS-CoV-2 pandemic situation, the timing between priming and boosting has emerged as a critical aspect of the vaccination program.…”

Section: Introductionmentioning

confidence: 99%

Short or Long Interval between Priming and Boosting: Does It Impact on the Vaccine Immunogenicity?

et al. 2021

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Characterizing the impact of the vaccination schedule on the induction of B and T cell immune responses is critical for improving vaccine immunogenicity. Here we compare the effect of a short (4 weeks) or a long (18 weeks) interval between priming and boosting in mice, using a model vaccine formulation based on the chimeric tuberculosis vaccine antigen H56 combined with alum. While no significant difference was observed in serum antigen-specific IgG response and the induction of antigen-specific T follicular helper cells into draining lymph nodes after the two immunization schedules, a longer interval between priming and boosting elicited a higher number of germinal center-B cells and H56-specific antibody-secreting cells and modulated the effector function of reactivated CD4+ T cells. These data show that the scheduling of the booster immunization could affect the immune response elicited by vaccination modulating and improving the immunogenicity of the vaccine.

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Section: Introductionmentioning

confidence: 99%

Short or Long Interval between Priming and Boosting: Does It Impact on the Vaccine Immunogenicity?

et al. 2021

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“…Additionally, the results showed that groups with late boosts had increased functionality and polyfunctionality scores relative to vaccine recipients with no late boost. Collectively, these results implied that additional boosting of the RV144 regimen with longer intervals between the initial vaccination and late boost could improve vaccine efficacy (48).…”

Section: Rv306 Phase 2 Trialmentioning

confidence: 86%

“…Rapid decline in protective antibody levels in most vaccine recipients led to the proposition that late boosts would induce durable protective immune response (88). Therefore, late boost studies (RV305 and RV306) were designed to assess immune responses generated in newly boosted vaccine recipients compared to RV144 vaccine recipients (47,48).…”

Section: Follow-up Studies Based On the Rv144 Trialmentioning

confidence: 99%

“…This study was designed to determine whether boosting the RV144 regimen at either month 12, 15, or 18 following initial vaccination would improve the quality, magnitude or duration of humoral, cellular, and mucosal responses. In addition, it was designed to also establish the optimal boosting interval for further clinical development (48). The study enrolled 367 healthy, HIVnegative individuals and randomly allocated them to one of five groups to receive vaccine or placebo.…”

Section: Rv306 Phase 2 Trialmentioning

confidence: 99%

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Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions

2020

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Following the discovery of HIV as a causative agent of AIDS, the expectation was to rapidly develop a vaccine; but thirty years later, we still do not have a licensed vaccine. Progress has been hindered by the extensive genetic variability of HIV and our limited understanding of immune responses required to protect against HIV acquisition. Nonetheless, valuable knowledge accrued from numerous basic and translational science research studies and vaccine trials has provided insight into the structural biology of the virus, immunogen design and novel vaccine delivery systems that will likely constitute an effective vaccine. Furthermore, stakeholders now appreciate the daunting scientific challenges of developing an effective HIV vaccine, hence the increased advocacy for collaborative efforts among academic research scientists, governments, pharmaceutical industry, philanthropy, and regulatory entities. In this review, we highlight the history of HIV vaccine development efforts, highlighting major challenges and future directions.

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“…Since the transcription of HIV genes depends on cell activation state, integrated HIV DNA is transcriptionally silent in these cells and therefore unaffected by ART [ 165 ]. Therefore, various cure strategies are proposed toward HIV cure ( Table 1 ) [ 114 , 116 , 117 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 ]. Of these, “shock and kill” and “block and lock” strategies are attempted to reactivate HIV-1 latency or to create a deep latent state.…”

Section: Strategies To Eradicate Viral Reservoirsmentioning

confidence: 99%

Residual Proviral Reservoirs: A High Risk for HIV Persistence and Driving Forces for Viral Rebound after Analytical Treatment Interruption

Wang

2021

Viruses

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Antiretroviral therapy (ART) has dramatically suppressed human immunodeficiency virus (HIV) replication and become undetectable viremia. However, a small number of residual replication-competent HIV proviruses can still persist in a latent state even with lifelong ART, fueling viral rebound in HIV-infected patient subjects after treatment interruption. Therefore, the proviral reservoirs distributed in tissues in the body represent a major obstacle to a cure for HIV infection. Given unavailable HIV vaccine and a failure to eradicate HIV proviral reservoirs by current treatment, it is crucial to develop new therapeutic strategies to eliminate proviral reservoirs for ART-free HIV remission (functional cure), including a sterilizing cure (eradication of HIV reservoirs). This review highlights recent advances in the establishment and persistence of HIV proviral reservoirs, their detection, and potential eradication strategies.

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Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial

Cited by 37 publications

References 29 publications

Short or Long Interval between Priming and Boosting: Does It Impact on the Vaccine Immunogenicity?

Short or Long Interval between Priming and Boosting: Does It Impact on the Vaccine Immunogenicity?

Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions

Residual Proviral Reservoirs: A High Risk for HIV Persistence and Driving Forces for Viral Rebound after Analytical Treatment Interruption

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