Douagi, I

Forsell, MM

Hedestam, GB Karlsson

Loré, K

Mascola, JR

O'dell, S

Seder, R

Sundling, C

Wyatt, RT

Retrovirology

English

PubMed

I Douagi

MM Forsell

C Sundling

S O'dell

R Seder

JR Mascola

K Loré

RT Wyatt

GB Hedestam

Springer - Publisher Connector

OA05-05. Impact of in vivo CD4 binding during HIV-1 Env trimer immunizations of rhesus macaques

GB Karlsson Hedestam

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BioMed CentralPage 1 of 1(page number not for citation purposes)RetrovirologyOpen AccessOral presentationOA05-05. Impact of in vivo CD4 binding during HIV-1 Env trimer immunizations of rhesus macaquesI Douagi*1, MM Forsell1, C Sundling1, S O'dell2, R Seder2, JR Mascola2, K Loré3, RT Wyatt2 and GB Karlsson Hedestam1Address: 1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden, 2Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA and 3Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden* Corresponding author    BackgroundWe recently reported that immunization with cleavage-defective soluble HIV-1 envelope glycoproteins (Env)trimers in monkeys, but not in rabbits, results in the elic-itation of antibodies directed against the co-receptor bind-ing site of gp120. This finding demonstrates that the highaffinity interaction between Env and primate CD4 resultsin an alteration of Env immunogenicity. To further inves-tigate the impact of Env-CD4 in vivo interactions duringvaccination, we immunized rhesus macaques with wildtype (wt) and CD4 binding defective Env trimers.MethodsGroups of five adult rhesus macaques were immunizedwith wt trimers or CD4 binding defective trimers, witheither retained or abrogated capacity to form the co-recep-tor binding-site. Plasma and PBMCs were collected 2weeks post-immunization. Frequency of Env-specific Band T cells were assessed by ELISpot analysis and flowcytometry. Serum antibodies were measured by ELISA andneutralization assays. Four weeks following the lastimmunization, control and vaccinated animals were chal-lenged with SHIVSF162P4.ResultsAntibodies against the co-receptor binding site were elic-ited in animals immunized with wt trimers, but not inanimals immunized with the CD4-binding defectivemutants. Elimination of the Env-CD4 in vivo interactiondid not affect vaccine-induced Env-specific T cellresponses or levels of total elicited binding antibodies.However, differences in the quality of the in vitro neutral-izing antibody response were observed between the threegroups. A comparable decrease in plasma viral loads com-pared to unvaccinated controls was also measured follow-ing challenge in all three groups.ConclusionThese results confirm that the wt Env trimers used hereinteract with host CD4 in vivo affecting the quality of theelicited antibody response. As Env-based vaccinesprogress from small animals to primates, the effects ofhigh affinity CD4 interaction may need to be consideredin regards to immunogen design.from AIDS Vaccine 2009Paris, France. 19–22 October 2009Published: 22 October 2009Retrovirology 2009, 6(Suppl 3):O35 doi:10.1186/1742-4690-6-S3-O35<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>This abstract is available from: http://www.retrovirology.com/content/6/S3/O35© 2009 Douagi et al; licensee BioMed Central Ltd. 

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OA05-05. Impact of in vivo CD4 binding during HIV-1 Env trimer immunizations of rhesus macaques

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