The purpose of this application is to facilitate the development of the candidate into an independent clinical investigator. The candidate has completed infectious diseases subspecialty training and epidemiology graduate studies and is seeking further mentor-guided training to attain the stated career goals. The overarching career goal is to develop a patient-oriented research program investigating vaccine-related host immunity to bioterrorism-associated and emerging viral infections, while becoming a successful independent clinician-researcher. The proposed career development plan consists of didactic training that will provide advanced immunology and biostatistics training, and mentored research to be conducted as a collaborative effort between Saint Louis University's Center for Vaccine Development and Washington University School of Medicine. The goal of the proposed research component is to translate novel immunology findings into the design and implementation of clinical studies evaluating vaccine-related host immunity to poxviruses.
The specific aims of the research are: To determine the kinetics of specific anti-vaccinia virus envelope protein antibodies post vaccinia virus vaccination and to correlate with smallpox immunity. To estimate smallpox herd immunity in a defined population.
The first aim will be accomplished by using an enzyme-linked immunosorbent assay (ELISA) to characterize the antibody responses to the specific vaccinia virus envelope proteins B5R, A33R, L1R, and A27L in individuals recently vaccinated with Modified Vaccinia Ankara (MVA) and Dryvax(r) vaccines. The specific antibody responses will be correlated to smallpox immunity by comparison to whole virus anti-vaccinia antibody titers, neutralizing antibody titers, and for Dryvax(r) recipients, presence of a major cutaneous reaction.
The second aim will be accomplished by performing a population-based serological survey in a midwestern metropolitan area to estimate the prevalence of antibody titers that are correlated with immunity. From these results smallpox herd immunity will be estimated. The results are expected to add to the body of knowledge regarding smallpox immunity generated by vaccinia virus immunization and to provide a baseline of normal human responses to specific vaccinia envelope proteins that are potential subunit vaccine candidates. ? ? ?
| Lawrence, Steven J; Lottenbach, Kathleen R; Newman, Frances K et al. (2007) Antibody responses to vaccinia membrane proteins after smallpox vaccination. J Infect Dis 196:220-9 |
