Sequential immunization with a subtype B HIV-1 envelope quasispecies partially mimics the in Vivo development of neutralizing antibodies

Delphine Malherbe, Nicole A. Doria-Rose, Lynda Misher, Travis Beckett, Wendy Blay Puryear, Jason T. Schuman, Zane Kraft, Jean O'Malley, Motomi (Tomi) Mori, Indresh Srivastava, Susan Barnett, Leonidas Stamatatos, Nancy Haigwood

Research output: Contribution to journalArticle

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Abstract

A major goal of human immunodeficiency virus type 1 (HIV-1) vaccine efforts is the design of Envelope (Env)-based immunogens effective at eliciting heterologous or broad neutralizing antibodies (NAbs). We hypothesized that programming the B-cell response could be achieved by sequentially exposing the host to a collection of env variants representing the viral quasispecies members isolated from an individual that developed broad NAbs over time. This ordered vaccine approach (sequential) was compared to exposure to a cocktail of env clones (mixture) and to a single env variant (clonal). The three strategies induced comparable levels of the autologous and heterologous neutralization of tier 1 pseudoviruses. Sequential and mixture exposure to quasispecies led to epitope targeting similar to that observed in the simian-human immunodeficiency virus (SHIV)-infected animal from which the env variants were cloned, while clonal and sequential exposure led to greater antibody maturation than the mixture. Therefore, the sequential vaccine approach best replicated the features of the NAb response observed in that animal. This study is the first to explore the use of a collection of HIV-1 env quasispecies variants as immunogens and to present evidence that it is possible to educate the B-cell response by sequential exposure to native HIV-1 quasispecies env variants derived from an individual with a broadened NAb response.

Original languageEnglish (US)
Pages (from-to)5262-5274
Number of pages13
JournalJournal of Virology
Volume85
Issue number11
DOIs
StatePublished - Jun 2011

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Cercopithecine Herpesvirus 1
Human immunodeficiency virus 1
Neutralizing Antibodies
neutralizing antibodies
HIV-1
Immunization
immunization
Vaccines
Pseudoviridae
vaccines
B-lymphocytes
B-Lymphocytes
antigens
Simian Immunodeficiency Virus
Human immunodeficiency virus
neutralization
epitopes
Epitopes
animals
Clone Cells

ASJC Scopus subject areas

  • Immunology
  • Virology

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Sequential immunization with a subtype B HIV-1 envelope quasispecies partially mimics the in Vivo development of neutralizing antibodies. / Malherbe, Delphine; Doria-Rose, Nicole A.; Misher, Lynda; Beckett, Travis; Puryear, Wendy Blay; Schuman, Jason T.; Kraft, Zane; O'Malley, Jean; Mori, Motomi (Tomi); Srivastava, Indresh; Barnett, Susan; Stamatatos, Leonidas; Haigwood, Nancy.

In: Journal of Virology, Vol. 85, No. 11, 06.2011, p. 5262-5274.

Research output: Contribution to journalArticle

Malherbe, D, Doria-Rose, NA, Misher, L, Beckett, T, Puryear, WB, Schuman, JT, Kraft, Z, O'Malley, J, Mori, MT, Srivastava, I, Barnett, S, Stamatatos, L & Haigwood, N 2011, 'Sequential immunization with a subtype B HIV-1 envelope quasispecies partially mimics the in Vivo development of neutralizing antibodies', Journal of Virology, vol. 85, no. 11, pp. 5262-5274. https://doi.org/10.1128/JVI.02419-10
Malherbe, Delphine ; Doria-Rose, Nicole A. ; Misher, Lynda ; Beckett, Travis ; Puryear, Wendy Blay ; Schuman, Jason T. ; Kraft, Zane ; O'Malley, Jean ; Mori, Motomi (Tomi) ; Srivastava, Indresh ; Barnett, Susan ; Stamatatos, Leonidas ; Haigwood, Nancy. / Sequential immunization with a subtype B HIV-1 envelope quasispecies partially mimics the in Vivo development of neutralizing antibodies. In: Journal of Virology. 2011 ; Vol. 85, No. 11. pp. 5262-5274.
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