Capturing viral diversity for in-vitro test reagents and HIV vaccine immunogen design

Berthou, Christian; Self, Steve; Korber, Bette T.

doi:10.1097/coh.0b013e3280f3bfe2

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…These studies highlight the importance of engineering Env immunogens that elicit a broader and more effective recognition of variant Env species compared with that achieved with an Env immunogen from a single viral isolate. Currently, the use of engineered ancestral or consensus Env sequences are being evaluated as immunogens to elicit immune responses (humoral and cellular) that can recognize a broad spectrum of HIV-1 variants within and between clades (18,49). An important aspect of the current experimental design is that the variant challenge virus envelopes reflected a valid ancestor relationship that is representative of the natural evolution observed in HIV-1 infections.…”

Section: Discussionmentioning

confidence: 99%

“…Studies on the effect of Env variation on antigenic properties indicate that even minor changes in amino acid sequence can dramatically alter antibody and CTL specificities in in vitro assays and immune control of persistent infections in vivo (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Nevertheless, even apparently extensive Env variations may not necessarily cause detectable changes in immune phenotype as measured by in vitro assays alone (18).…”

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confidence: 99%

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Envelope variation as a primary determinant of lentiviral vaccine efficacy

Craigo

Zhang

Barnes

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Lentiviral envelope antigenic variation and associated immune evasion are believed to present major obstacles to effective vaccine development. Although this perception is widely assumed by the scientific community, there is, to date, no rigorous experimental data assessing the effect of increasing levels of lentiviral Env variation on vaccine efficacy. It is our working hypothesis that Env is, in fact, a primary determinant of vaccine effectiveness. We previously reported that a successful experimental attenuated equine infectious anemia virus vaccine, derived by mutation of the viral S2 accessory gene, provided 100% protection from disease after virulent virus challenge. Here, we sought to comprehensively test our hypothesis by challenging vaccinated animals with proviral strains of defined, increasing Env variation, using variant envelope SU genes that arose naturally during experimental infection of ponies with equine infectious anemia virus. The reference attenuated vaccine combined with these variant Env challenge strains facilitated evaluation of the protection conferred by ancestral immunogens, because the Env of the attenuated vaccine is a direct ancestor to the variant proviral strain Envs. The results demonstrated that ancestral Env proteins did not impart broad levels of protection against challenge. Furthermore, the results displayed a significant inverse linear correlation of Env divergence and protection from disease. This study demonstrates potential obstacles to the use of single isolate ancestral Env immunogens. Finally, these findings reveal that relatively minor Env variation can pose a substantial challenge to lentiviral vaccine immunity, even when attenuated vaccines are used that, to date, achieve the highest levels of vaccine protection.ancestral immunogen ͉ equine infectious anemia virus ͉ lentivirus

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Envelope variation as a primary determinant of lentiviral vaccine efficacy

Craigo

Zhang

Barnes

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…For this reason, different test antigen design strategies, trying to cope with the diversity of circulating viral isolates in a single sequence, have been developed in the past. These strategies include central sequence designs such as Center of Tree (COT) [ 28 , 29 , 30 , 31 , 32 ], Ancestral [ 33 , 34 , 35 , 36 ] or Consensus sequences [ 29 , 30 , 31 , 32 , 35 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]; which may (Ancestral, COT) or may not (Consensus) represent naturally occurring sequences of replication competent viruses. All these designs are sensitive to the underlying sequence database and may change over time as new sequence information on additional isolates becomes available.…”

Section: Introductionmentioning

confidence: 99%

“…All these designs are sensitive to the underlying sequence database and may change over time as new sequence information on additional isolates becomes available. Direct comparisons of these different central sequence approaches have been performed for a highly variable pathogen (human immunodeficiency virus, HIV) and shown that the different designs yielded comparable results when synthetic peptides covering these sequences were used to measure virus-specific T cell responses [ 42 , 43 ]. However, the additional costs in terms of peptide synthesis and cells needed for ex-vivo experiments, may not warrant inclusion of all the different variants into a single test set.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Consensus-Sequence and Matching Overlapping Peptides Design for COVID19 Immune Studies and Vaccine Development

et al. 2020

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Synthetic antigens based on consensus sequences that represent circulating viral isolates are sensitive, time saving and cost-effective tools for in vitro immune monitoring and to guide immunogen design. When based on a representative sequence database, such consensus sequences can effectively be used to test immune responses in exposed and infected individuals at the population level. To accelerate immune studies in SARS-CoV-2 infection, we here describe a SARS-CoV-2 2020 consensus sequence (CoV-2-cons) which is based on more than 1700 viral genome entries in NCBI and encompasses all described SARS-CoV-2 open reading frames (ORF), including recently described frame-shifted and length variant ORF. Based on these sequences, we created curated overlapping peptide (OLP) lists containing between 1500 to 3000 peptides of 15 and 18 amino acids in length, overlapping by 10 or 11 residues, as ideal tools for the assessment of SARS-CoV-2-specific T cell immunity. In addition, CoV-2-cons sequence entropy values are presented along with variant sequences to provide increased coverage of the most variable sections of the viral genome. The identification of conserved protein fragments across the coronavirus family and the corresponding OLP facilitate the identification of T cells potentially cross-reactive with related viruses. This new CoV-2-cons sequence, together with the peptides sets, should provide the basis for SARS-CoV-2 antigen synthesis to facilitate comparability between ex-vivo immune analyses and help to accelerate research on SARS-CoV-2 immunity and vaccine development.

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