title: Envelope vaccination shapes viral envelope evolution following simian immunodeficiency virus infection in rhesus monkeys.
abstract: The evolution of envelope mutations by replicating primate immunodeficiency viruses allows these viruses to escape from the immune pressure mediated by neutralizing antibodies. Vaccine-induced anti-envelope antibody responses may accelerate and/or alter the specificity of the antibodies, thus shaping the evolution of envelope mutations in the replicating virus. To explore this possibility, we studied the neutralizing antibody response and the envelope sequences in rhesus monkeys vaccinated with either gag-pol-nef immunogens or gag-pol-nef immunogens in combination with env and then infected with simian immunodeficiency virus (SIV). Using a pseudovirion neutralization assay, we demonstrate that envelope vaccination primed for an accelerated neutralizing antibody response following virus challenge. To monitor viral envelope evolution in these two cohorts of monkeys, full-length envelopes from plasma virus isolated at weeks 37 and 62 postchallenge were sequenced by single genome amplification to identify sites of envelope mutations. We show that env vaccination was associated with a change in the pattern of envelope mutations. Prevalent mutations in sequences from gag-pol-nef vaccinees included deletions in both variable regions 1 and 4 (V1 and V4), whereas deletions in the env vaccinees occurred only in V1. These data show that env vaccination altered the focus of the antibody-mediated selection pressure on the evolution of envelope following SIV challenge.
authors.affiliation: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Aravind
authors.initials: A
authors.lastname: Basavapathruni
authors.forename: Wendy W
authors.initials: WW
authors.lastname: Yeh
authors.forename: Rory T
authors.initials: RT
authors.lastname: Coffey
authors.forename: James B
authors.initials: JB
authors.lastname: Whitney
authors.forename: Peter T
authors.initials: PT
authors.lastname: Hraber
authors.forename: Ayush
authors.initials: A
authors.lastname: Giri
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Srinivas S
authors.initials: SS
authors.lastname: Rao
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing; D002460:Cell Line; D019143:Evolution, Molecular; D006801:Humans; D008253:Macaca mulatta / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D018449:SAIDS Vaccines; D014759:Viral Envelope Proteins