In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay. IgG levels to these antigens were assessed as correlates of risk in vaccine recipients using weighted logistic regression models. Levels of Abs reactive with subtype A, B, C and CRF01_AE V1V2-scaffold antigens were all significant inverse correlates of risk (p-values of 0.0008–0.05; estimated odds ratios of 0.53–0.68 per 1 standard deviation increase). Thus, levels of vaccine-induced IgG Abs recognizing V1V2 regions from multiple HIV-1 subtypes, and presented on different scaffolds, constitute inverse correlates of risk for HIV-1 infection in the RV144 vaccine trial. The V1V2 antigens provide a link between RV144 and upcoming HIV-1 vaccine trials, and identify reagents and methods for evaluating V1V2 Abs as possible correlates of protection against HIV-1 infection.Trial RegistrationClinicalTrials.gov NCT00223080

To evaluate antibody specificities induced by simian immunodeficiency virus (SIV) versus human immunodeficiency virus type 1 (HIV-1) envelope antigens in nonhuman primate (NHP), we profiled binding antibody responses to linear epitopes in NHP studies with HIV-1 or SIV immunogens. We found that, overall, HIV-1 Env IgG responses were dominated by V3, with the notable exception of the responses to the vaccine strain A244 Env that were dominated by V2, whereas the anti-SIVmac239 Env responses were dominated by V2 regardless of the vaccine regimen.

Because current treatments for preterm labor are either unsafe or ineffective and bacteria‐induced preterm labor is the leading cause of premature birth, here, we sought to test whether use of a natural product with anti‐bacterial and ‐inflammatory activities and a long history of safe use, namely Echinacea purpurea (L.) Moench (whole hydro‐ethanolic), could be used to attenuate bacteria‐ (lipopolyssacharide, LPS)‐induced inflammation in the mice uterine cervix. We initially optimized routes and dosages of the extract, and then deciphered the likely underlying mechanism by treating animals with either vehicle only, or a combination of whole hydro‐ethanolic root extract, LPS, and/or heme‐oxygenase 1 (HO‐1) inhibitor, dose‐dependently. Tissues were then harvested and evaluated using real time‐PCR, Western blot, histology and confocal immunofluorescence. Our data show that the extract promotes expression of HO‐1 mRNA and HO‐1 inhibitor blocked the protective effects of the extract in animals treated with LPS, dose‐dependently. We conclude from these findings that Echinacea could potentially be used to modulate inflammation‐induced preterm labor and that HO‐1 may mediate the anti‐inflammatory activities of E. purpurea in the uterine cervix. Funding: Office of Students Research, Appalachian State University.