Developing an HIV vaccine

Haynes, Barton F.; Burton, Dennis R.

doi:10.1126/science.aan0662

Cited by 92 publications

(86 citation statements)

References 15 publications

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“…Moreover, bnAb induction may occur with Env vaccination in the presence of Ig LC repertoire holes and default to less disfavored neutralizing antibody specificities such as V1V2-glycan bnAbs. The next steps are optimizing Env structures and/or sequential Envs, as well as reducing host constraints on bnAb generation to expand the frequency of bnAb responses in nonhuman primates, and ultimately in humans (Haynes and Burton, 2017). …”

Section: Discussionmentioning

confidence: 99%

Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models

Saunders

Verkoczy

Jiang³

et al. 2017

Cell Reports

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147

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SUMMARY The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof-of-concept would be critical. Here, we describe the induction of plasma antibodies capable of neutralizing heterologous primary (tier 2) HIV-1 strains in one macaque and two rabbits. Env immunogens were designed to induce CD4 binding site (CD4bs) bnAbs, but surprisingly, the macaque developed V1V2-glycan bnAbs. Env immunization of CD4bs bnAb heavy chain rearrangement (VHDJH) knock-in mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs VH chains were replaced with mouse rearrangements bearing diversity region (D)-D fusions, creating antibodies with long, tyrosine-rich HCDR3s. Our results show Env vaccination can elicit broad neutralization of tier 2 HIV-1, demonstrate V1V2 glycan bnAbs are more readily induced than CD4bs bnAbs, and define VH replacement and diversity region fusion as potential mechanisms for generating V1V2-glycan bnAb site antibodies.

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Section: Discussionmentioning

confidence: 99%

Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models

Saunders

Verkoczy

Jiang³

et al. 2017

Cell Reports

Self Cite

147

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“…Exceptional features of bNAbs inspire many researches to develop immunogen capable of their producing (induction). One of the evolving research areas focusing on the design of such immunogens is based on the development of HIV-1 envelope (Env) trimers [6,[34][35][36].…”

Section: B-cell Epitopes To Hiv-1 Generating Broadly Neutralizing Antmentioning

confidence: 99%

“…Thirdly, virus proteins include regions with pathogenic properties due to molecular mimicry of physiologically significant functions or induction of autoimmune responses that might contribute to immunodeficiency. Finally, when studying HIV-infection, experimental models are very limited [1,[5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Artificial Epitope-Based Immunogens in HIV-Vaccine Design

Karpenko¹,

Bazhan²,

Eroshkin³

et al. 2018

Advances in HIV and AIDS Control

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One of the promising approaches for designing HIV vaccines is construction of synthetic polyepitope HIV-1 immunogen using a wide range of conservative T-and B-cell epitopes of the main virus antigens. In theory this approach helps cope with HIV-1 antigenic variability, focuses immune responses on protective determinants and enables to exclude from the vaccine compound adverse regions of viral proteins that can induce autoantibodies or antibodies enhancing infectivity of virus. The paper presents the experience of our team in development of artificial polyepitope HIV-1 immunogens, which can induce both a humoral response, and responses of cytotoxic (CD8 + CTL) and helpers (CD4 + Th) T-cells. The design of HIV-immunogens has been done using our original software, TEpredict and PolyCTLDesigner. We describe development of the candidate HIV-1/ AIDS vaccine-CombiHIVvac, which included two artificial polyepitope immunogens TBI and TCI for stimulating humoral and cellular responses. The results of the specific activity and safety of CombiHIVvac vaccine, obtained during preclinical and clinical trials, are presented.

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“…Despite major advances in antiretroviral therapy (ART) against HIV‐1, an inspired global commitment will be required to end the epidemic by 2030 (http://www.unaids.org/en/resources/fact-sheet). Unfortunately, developing an effective vaccine has been very challenging for reasons related to the nature of the HIV‐1 virion . Of several vaccine concepts tested in efficacy trials, only one, the RV144 pox virus prime, protein boost (ALVAC/AIDSVAX B/E) vaccine, showed a low level of vaccine protection with an estimated 31% vaccine efficacy …”

Section: Role Of Mass Spectrometry In the Vaccine Developmentmentioning

confidence: 99%

The expanding role of mass spectrometry in the field of vaccine development

Sharma

Sharma²,

Glick

2018

Mass Spectrometry Reviews

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Biological mass spectrometry has evolved as a core analytical technology in the last decade mainly because of its unparalleled ability to perform qualitative as well as quantitative profiling of enormously complex biological samples with high mass accuracy, sensitivity, selectivity and specificity. Mass spectrometry-based techniques are also routinely used to assess glycosylation and other post-translational modifications, disulfide bond linkage, and scrambling as well as for the detection of host cell protein contaminants in the field of biopharmaceuticals. The role of mass spectrometry in vaccine development has been very limited but is now expanding as the landscape of global vaccine development is shifting towards the development of recombinant vaccines. In this review, the role of mass spectrometry in vaccine development is presented, some of the ongoing efforts to develop vaccines for diseases with global unmet medical need are discussed and the regulatory challenges of implementing mass spectrometry techniques in a quality control laboratory setting are highlighted.

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Developing an HIV vaccine

Abstract: What are the paths and obstacles to a practical vaccine?

Cited by 92 publications

References 15 publications

Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models

Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models

Artificial Epitope-Based Immunogens in HIV-Vaccine Design

The expanding role of mass spectrometry in the field of vaccine development

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