DNA/long peptide vaccination against conserved regions of SIV induces partial protection against SIVmac251 challenge

Koopman, Gerrita; Beenhakker, Nielsa; Nieuwenhuis, Ivonnea; Doxiadis, Gabyb; Mooij, Petraa; Drijfhout, Jan W.c; Koestler, Josefd; Hanke, Tomase; Fagrouch, Zahraa; Verschoor, Ernst J.a; Bontrop, Ronald E.b; Wagner, Ralfd; Bogers, Willy M.J.M.a; Melief, Cornelis J.M.c,f

AIDS:
doi: 10.1097/QAD.0000000000000047
Basic Science
Abstract

Objectives: We recently developed a HIVconsv vaccine strategy, consisting of combined conserved regions of HIV-1, to adequately cover viral diversity. To evaluate efficacy in nonhuman primates, an equivalent SIV-derived immunogen SIVconsv was designed and delivered as plasmid DNA or synthetic long peptides.

Design: Rhesus macaques lacking protective MHC class I alleles Mamu-A*001 : 01, B*008 : 01, B*017 : 01 were immunized with either SIVconsv synthetic long peptides (S) alone or in combination with plasmid DNA encoding the same conserved regions (D) using SSS or DDSS regimens.

Methods: The SIVconsv synthetic long peptide vaccine consisted of 46 approximately 30-amino acid-long peptides emulsified in Montanide ISA-720 and adjuvanted with pegylated type I interferon and imiquimod.

Results: Both SSS and DDSS regimens generated high frequencies of SIV-specific IFN-γ-producing cells comparable with reported adenoviral vector systems. Strong polyfunctional CD4+ T-cell and modest CD8+ T-cell responses were generated, which were of central memory T-cell phenotype. Furthermore, SIVconsv-specific antibody responses were induced capable of recognizing the Env glycoprotein. Eight weeks after the last immunization, control and SIVconsv-vaccinated animals were challenged intrarectally with 10 MID50 of pathogenic SIVmac251. Two out of six animals in the DDSS group were protected against infection, while all 14 animals in the SSS and two control groups were infected. Vaccine induced SIV-specific IgG responses in mucosal washes prechallenge were highest in the two protected animals.

Conclusion: This study demonstrates that vaccine-elicited responses towards conserved regions can afford partial protection against a high-dose intrarectal SIVmac251 challenge.

Author Information

aDepartment of Virology

bDepartment of Comparative Genetics and Refinement, Biomedical Primate Research Centre, Rijswijk

cDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands

dUniversity of Regensburg, Regensburg, Germany

eThe Jenner Institute, University of Oxford, Oxford, UK

fISA Pharmaceuticals, Leiden, the Netherlands.

Correspondence to Dr G. Koopman, Biomedical Primate Research Centre, Department of Virology, Lange Kleiweg 161, 2288 GJ Rijswijk, the Netherlands. Tel: +31 152842761; fax: +31 152842660; e-mail: koopman@bprc.nl

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© 2013 Lippincott Williams & Wilkins, Inc.