A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence.

Transmitted/founder (T/F) HIV-1 envelope proteins (Envs) from infected individuals that developed neutralization breadth are likely to possess inherent features desirable for vaccine immunogen design. To explore this premise, we conducted an immunization study in rhesus macaques (RM) using T/F Env sequences from two human subjects, one of whom developed potent and broad neutralizing antibodies (Z1800M) while the other developed little to no neutralizing antibody responses (R66M) during HIV-1 infection. Using a DNA/MVA/protein immunization protocol, 10 RM were immunized with each T/F Env. Within each T/F Env group, the protein boosts were administered as either monomeric gp120 or stabilized trimeric gp140 protein. All vaccination regimens elicited high titers of antigen-specific IgG, and two animals that received monomeric Z1800M Env gp120 developed autologous neutralizing activity. Using early Env escape variants isolated from subject Z1800M as guides, the serum neutralizing activity of the two immunized RM was found to be dependent on the gp120 V5 region. Interestingly, the exact same residues of V5 were also targeted by a neutralizing monoclonal antibody (nmAb) isolated from the subject Z1800M early in infection. Glycan profiling and computational modeling of the Z1800M Env gp120 immunogen provided further evidence that the V5 loop is exposed in this T/F Env and was a dominant feature that drove neutralizing antibody targeting during infection and immunization. An expanded B cell clonotype was isolated from one of the neutralization-positive RM and nmAbs corresponding to this group demonstrated V5-dependent neutralization similar to both the RM serum and the human Z1800M nmAb. The results demonstrate that neutralizing antibody responses elicited by the Z1800M T/F Env in RM converged with those in the HIV-1 infected human subject, illustrating the potential of using immunogens based on this or other T/F Envs with well-defined immunogenicity as a starting point to drive breadth.

Is Oral Biopsy Associated With Change in Tobacco or Alcohol Use?

PURPOSE: Tobacco and alcohol remain the predominant risk factors for oral cancer, but the relation between having an oral biopsy and cessation of these risk factors is unknown. Therefore, this investigation examined whether there might be an association between oral biopsy and change in risk factor use. MATERIALS AND METHODS: A survey was sent to a cohort consisting of a consecutive sample of subjects identified in the University of North Carolina Oral Pathology database. The predictor variable was oral biopsy diagnosis, with 3 levels consisting of hyperkeratosis, dysplasia, or carcinoma. The outcome variable was change in risk factor use, coded as "no change in usage," "decreased usage" or "quit." Other study variables included age, gender, and race. The proportional odds model was used to assess the effect of explanatory variables on change in use, and the P value was set at .05. RESULTS: The response rate was 37.4% for a total sample of 605 subjects. White non-Hispanics composed 85% of respondents and women composed 49.5%, with no significant difference among diagnostic categories. The global test for change in cigarette use was significant, with age contributing to variability in behavioral change. Although not statistically significant, larger percentages of patients with more severe diagnoses quit cigarettes and alcohol following biopsy. The youngest respondents were 3.7 times more likely not to quit before biopsy or to continue to smoke following biopsy (95% confidence interval, 1.98-6.91). CONCLUSION: The results of this study suggest that oral biopsy provides an ideal opportunity to focus on risk factor cessation. Different diagnoses provide objective data on which to base a discussion about carcinogenesis and the roles played by the risk factors in this process. Differences in risk factor cessation associated with demographics emphasize the need for all clinicians to address cessation with all patients.