87,p=0

87,p=0.0078, respectively) (Fig. and IgG3. Antibody responses to gp120 A244gD, MNgD, and gp70V1V2 92TH023 scaffold were significantly higher in RV135 than in RV132. Antibodies to gp70V1V2 CaseA2 were detected only in RV135 vaccine recipients and IgG1 and IgG3 antibody responses to A244gD were significantly higher in RV135. IgG binding to gp70V1V2 CaseA2 and CRF01_AE scaffolds was higher with the AIDSVAXB/E boost but both trials showed similar rates of antibody decline post-vaccination. MF59 did not result in higher IgG antibody responses compared to alum with the antigens tested. However, notable differences in the structure of the recombinant proteins and dosage used for immunizations may have contributed to the magnitude and specificity of IgG induced by the two trials. == Introduction == The Thai PhaseIIItrial, RV144, showed an estimated vaccine efficacy of 31.2% at 42 months, and post hoc analysis suggested that efficacy at 12 months was 60% (95% CI 280%).1,2The vaccine regimen consisted of a nonreplicating recombinant canarypox vector, ALVAC-HIV (vCP1521) primary and AIDSVAXgp120 B/E boost. The vaccine-induced plasma IgG binding antibody to scaffolded gp70V1V2 envelope proteins from multiple HIV-1 subtypes correlated inversely while high levels of Env plasma IgA (monomeric) binding score correlated directly with HIV acquisition.35Viral sieve analysis backed a role for the second variable domain of Env (V2) in protection.6Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that NF2 this vaccination regimen induced antibody responses to the V2 loop of gp120 of multiple subtypes. V2 responses by ELISA and surface plasmon resonance were further evaluated using cyclic (CycV2) and linear V2 loop peptides. Ninety-seven percent of volunteers experienced antibody responses against CycV2 at 2 weeks post-last immunization, declining to 19% 6 months later.7 Whether quantitative and qualitative antibody responses to soluble HIV-1 envelope (Env) protein subunits can be modulated by adjuvants remains a critical question for the selection of Env immunogens in future efficacy trials.8,9We investigated HIV-specific binding antibody AMG 337 responses to whole gp120 proteins, gp70V1V2 scaffolds, a CycV2 peptide, AMG 337 and IgG subclasses in two phase I/II prime-boost vaccine trials conducted in Thailand prior to RV144 (RV13510and RV13211). RV135 was the phase I/II forerunner to RV144 with the identical vaccine components and immunization regimen. Both trials used ALVAC-HIV (vCP1521) as a primary and each used a different bivalent HIV-1 gp120 protein boost formulated either in alum (RV135) or in MF59 (RV132) adjuvant. == Materials and Methods == == Vaccines and immunization regimens == ALVAC-HIV (vCP1521) (Sanofi Pasteur, Marcy-l’Etoile, France) is a recombinant canarypox AMG 337 vector genetically designed to express Env gp120 of the HIV-1 CRF01_AE 92TH023 strain linked to the transmembrane anchoring portion of subtype B gp41 (with a deletion in the immunodominant region devoid of the entire gp41 ectodomain), and HIV-1 Gag and protease (both LAI strain). ALVAC-HIV (vCP1521) was administered at a dose of 106.5CCID50. AIDSVAXB/E vaccine (Global Solutions for Infectious Diseases, GSID, South San Francisco, CA) used in both RV144 and RV135 is composed of gp120 HIV-1 subtype B MN and HIV-1 gp120 CRF01_AE A244, each made up of a 27 amino acid (aa) sequence from your herpes simplex virus gD protein fused to each protein at the N-terminus. MNgD AMG 337 and A244gD gp120 proteins were expressed in CHO cells, adsorbed onto aluminium hydroxide gel adjuvant, and combined to produce the bivalent AIDSVAXB/E vaccine administered at 600 g (300 g of each rgp120).1,10,12Bivalent gp120 B/CRF01_AE vaccine used in RV132 was also produced in CHO cells (Novartis Vaccines and Diagnostics, Cambridge, MA) and contained 100 g of gp120 from your CRF01_AE strain CM235 and 50 g from your subtype B strain SF2, formulated in MF59 adjuvant.11Both trials used the same immunization schedule used in RV144, with administration of ALVAC-HIV at 0, 1, 3, and 6 months and gp120 protein boosts at 3 and 6 months. == Specimens and study subjects == Plasma samples from 15 vaccine and 6 placebo recipients (RV132) and 30 vaccine and 10 placebo recipients (RV135) were randomly selected. Both studies experienced received approval of appropriate Institutional Review Boards and written informed consent was obtained from all volunteers. Samples were tested at baseline, 2 weeks post-second ALVAC vaccination, 2 weeks post-third and fourth vaccinations (protein boosts), AMG 337 and 6 months post-fourth vaccination. All participants were HIV-1 uninfected at the time of blood draw. All plasma and serum specimens were stored at 80C. == Recombinant proteins and CycV2 peptide.