HIV-1 Immunogen: an overview of almost 30 years of clinical testing of a candidate therapeutic vaccine

Graziani, Gina M.; Angel, Jonathan B.

doi:10.1080/14712598.2016.1193594

Cited by 7 publications

(6 citation statements)

References 38 publications

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“…Consequently, no inactivated HIV-1 vaccine for prophylaxis have been tested so far in phase-I to -III human trials according to IAVA database [ 31 ]. However, inactivated HIV-1 vaccine has been tested as therapeutic vaccine in HIV-positive (HIV + ) subjects [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine

Sahay

Yamamoto

2018

Viruses

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The feline immunodeficiency virus (FIV) vaccine called Fel-O-Vax® FIV is the first commercial FIV vaccine released worldwide for the use in domestic cats against global FIV subtypes (A–E). This vaccine consists of inactivated dual-subtype (A plus D) FIV-infected cells, whereas its prototype vaccine consists of inactivated dual-subtype whole viruses. Both vaccines in experimental trials conferred moderate-to-substantial protection against heterologous strains from homologous and heterologous subtypes. Importantly, a recent case-control field study of Fel-O-Vax-vaccinated cats with outdoor access and ≥3 years of annual vaccine boost, resulted in a vaccine efficacy of 56% in Australia where subtype-A viruses prevail. Remarkably, this protection rate is far better than the protection rate of 31.2% observed in the best HIV-1 vaccine (RV144) trial. Current review describes the findings from the commercial and prototype vaccine trials and compares their immune correlates of protection. The studies described in this review demonstrate the overarching importance of ant-FIV T-cell immunity more than anti-FIV antibody immunity in affording protection. Thus, future efforts in developing the next generation FIV vaccine and the first effective HIV-1 vaccine should consider incorporating highly conserved protective T-cell epitopes together with the conserved protective B-cell epitopes, but without inducing adverse factors that eliminate efficacy.

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Section: Introductionmentioning

confidence: 99%

Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine

Sahay

Yamamoto

2018

Viruses

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“…Several approaches have been pursued to elicit bNAbs. One approach aims to design immunogens that could better mimic bNAb epitopes . Another approach uses B‐cell lineage vaccine strategy to design specific immunogens that target the desired precursors of bNAb‐producing cells, allowing the maturation of B‐cells through uncommon pathways .…”

Section: Four Hiv‐1 Vaccine Strategies From Completed Phase Iib or IImentioning

confidence: 99%

Synthetic biology approach for the development of conditionally replicating HIV-1 vaccine

Wang

Yuan

Niu

et al. 2017

J. Chem. Technol. Biotechnol

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While the combined antiretroviral therapy has resulted in a significant decrease in HIV-1 related morbidity and mortality, the HIV-1 pandemic has not been substantially averted. To curtail the 2.4 million new infections each year, a prophylactic HIV-1 vaccine is urgently needed. This review first summarizes four major completed clinical efficacy trials of prophylactic HIV-1 vaccine and their outcomes. Next, it discusses several other approaches that have not yet advanced to clinical efficacy trials, but provided valuable insights into vaccine design. Among them, live-attenuated vaccines (LAVs) provided excellent protection in a non-human primate model. However, safety concerns have precluded the current version of LAVs from clinical application. As the major component of this review, two synthetic biology approaches for improving the safety of HIV-1 LAVs through controlling HIV-1 replication are discussed. Particular focus is on a novel approach that uses unnatural amino acid-mediated suppression of amber nonsense codon to generate conditionally replicating HIV-1 variants. The objective is to attract more attention towards this promising research field and to provoke creative designs and innovative utilization of the two control strategies.

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“…To achieve sustained virologic control of HIV-1 (ART-free HIV remission) and to clear virus-expressing cells, it is likely that immune-based therapies will be needed. Therapeutic HIV vaccine trials in chronic HIV infection have been met with little success in regard to clinical benefits [ 40 ]. There are strong rationales for studying therapeutic HIV vaccines in early-treated individuals who have few or no viral escape, less CD4 + depletion and more preserved memory T cells.…”

Section: Effects Of Early Antiretroviral Therapy and Relevance To Thementioning

confidence: 99%

Lessons from acute HIV infection

Robb

Ananworanich

2016

Current Opinion in HIV and AIDS

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Purpose of reviewUnderstanding the characteristics of transmission during acute HIV infection (AHI) may inform targets for vaccine-induced immune interdiction. Individuals treated in AHI with a small HIV reservoir size may be ideal candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic control after treatment interruption).Recent findingsThe AHI period is brief and peak viremia predicts a viral set point that occurs 4–5 weeks following infection. Robust HIV-specific CD8+ T-cell responses lower viral set points. Phylogenetic analyses of founder viruses demonstrated unique bottleneck selections and specific genetic signatures to optimize for high-fitness variants and successful transmission events. HIV clades, route of transmission and the presence of minor variants may affect vaccine protection. Antiretroviral treatment in AHI results in smaller HIV reservoir size, better CD4+ T-cell recovery and fewer virus escapes.SummaryThe knowledge of untreated and treated AHI informs the development of vaccines, in that preventive vaccines will require broad coverage for multiple clades and antigenic variants associated with unique bottleneck selections. Vaccines that help the host to control viremia could minimize onward transmission. Therapeutic HIV vaccines aimed at HIV remission should be studied in early-treated individuals who have few or no viral escape mutants and a more preserved immune system.

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HIV-1 Immunogen: an overview of almost 30 years of clinical testing of a candidate therapeutic vaccine

Cited by 7 publications

References 38 publications

Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine

Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine

Synthetic biology approach for the development of conditionally replicating HIV-1 vaccine

Lessons from acute HIV infection

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