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Immunogenicity and Efficacy of ALVAC-HIV/gp120-Clade C in Alum Regimen in Macaques
Luca Schifanella1; David Venzon1; Susan Barnett2; Sanjay Phogat3; Georgia Tomaras4; David Montefiori4; Massimiliano Bissa1; Veronica Galli1; Ruth M. Ruprecht5; Genoveffa Franchini1
1NIH, Bethesda, MD, USA;2Novartis, Cambridge, MA, USA;3Sanofi, Swiftwater, PA, USA;4Duke Univ, Durham, NC, USA;5Texas Biomed Rsr Inst, San Antonio, TX, USA
The RV144, a phase 3 trial held in Thailand, reduced the risk of HIV infection by 31.2%. In our lab we replicated the results of this study in a SIVmac251 models using an ALVAC/SIV-gp120/Alum Alhydrogel vaccine (44% vaccine efficacy). A trial has begun in South Africa (SA) to test a similar vaccine using clade C immunogens. We design a study in which we tested the ALVAC HIV/gp120 Clade C Alum in macaques model
27 all-female Indian rhesus macaques received at weeks (wk) 0, 4, 12 and 24 intramuscularly 10^8 PFU of both ALVAC vCP172 expressing SIV gag-pol and another and ALVAC vCP1521 expressing ZM96 Clade C HIV gp120 env trans-membrane anchor and the Clade B gag, pro. 200μg of each gp120 (TV1 and 1086) in alum hydroxide (proprietary formulation) were given at weeks 12 and 24. 20 controls received only Alum. 4 wk after last immunization, all the animals were challenged with repeated low doses SHIV1157ipd3N4 via vaginal route 17 times
Plasmablasts (PBs) frequency increased 1 wk after the last vaccination (p=0.0005) while the α4β7 subset decreased (p=0.0010) and the CXCR3+ did not changed. Serum antibodies titer to 1086 peaked at week 26 (>10^6) in vaccinated animals that did not became infected and maintained a title > then 10^4 up to 48 wks. Plasma Abs elicited were able to neutralize only tier 1 Clade C viruses. Mucosal antibodies to V2 were higher in the vaginal mucosa then in the rectal. PBs CXCR3+ correlated with antibodies to V1/V2 antigens. Surprisingly we observed no reduction in the risk of SHIV acquisition in the vaccinated animals, nor protection from high viral load, nor CD4 loss. However animals that were infected later had higher titer of Ab titer in plasma at wk 28 to 1086
The lack of vaccine effect was surprising given the efficacy observed in a similar vaccine tested in the SIVmac251 model. However the α4β7 plasmablasts frequency differed in the two vaccine regimens. This difference might be due to differences in the adjuvants used in the two vaccine regimes that might also influenced differences in vaccine efficacy.