# Mechanisms of Humoral Immune Protection Induced by Anthrax Vaccine Adsorbed

> **NIH NIH U19** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2020 · $463,182

## Abstract

Project Summary
To mitigate the ongoing threat of anthrax infection due to bioterrorism, active military members are vaccinated
with Anthrax Vaccine Adsorbed (AVA). However, some AVA recipients may remain unprotected against
anthrax infection and a better understanding of mechanisms leading to impaired vaccine response and rapidly
waning immunity are needed. In the largest real-world cohort of AVA vaccinees (>2,900 individuals), less than
50% of AVA vaccinees showed significant in vitro lethal toxin neutralization, and both antibody levels and
neutralization capacity waned quickly after vaccination. Therefore, the goal of this project is to identify
mechanisms of poor neutralization after AVA vaccination. The primary antigen in AVA is protective antigen
(PA). Our previous studies have identified common sequential epitopes recognized by serum anti-PA, and
have shown differential epitope binding of neutralizing vs. non-neutralizing responses. Poorly neutralizing
responses have also been associated with impaired avidity of anti-PA and enhanced IgG4 production. In
addition, suboptimal AVA responses are more common in African American vs. European American vaccinees.
Preliminary data suggest that African American individuals have enriched responses against non-neutralizing
epitopes after AVA vaccination and have marked differences in immune cell subsets and immune pathways
compared to European American individuals. Critical questions remain in understanding the mechanisms of
rapidly waning or impaired adult vaccination responses, such as those against AVA. This project addresses
mechanisms of impaired protection after AVA immunization by comparing anti-PA antibodies from high and low
neutralizers in the AVA cohort described above as well as new recruits for domain specificity, anti-PA avidity,
and anti-PA IgG4 responses, all of which may inhibit protective human Bacillus anthracis immunity (Aim 1).
Additional mechanisms of protective responses will be dissected using neutralizing PA-specific human
monoclonal antibodies previously generated by our lab. In addition, although anti-PA domain specificity is
related to neutralizing capacity, the conformational epitopes of PA bound by the serum of neutralizers have not
been elucidated. Therefore, this project uses novel hydrogen-deuterium exchange mass spectrometry tech-
niques to map anti-PA binding sites on PA using sera from high and low neutralizers (Aim 2). Finally, mech-
anisms of impaired AVA responses will be evaluated in African American vs. European American vaccinees
(Aim 3). Antibodies, immune cell profiles, and regulatory pathways will be compared by mass cytometry
(CyTOF), intracellular cytokine production, flow cytometry and ELISpot at various times after AVA vaccination.
Epitope specificity and genetic predisposition to impaired anti-PA responses will be tested. These studies will
provide new insights to optimize future anthrax vaccines and other adult vaccinations across racial groups.

## Key facts

- **NIH application ID:** 9927977
- **Project number:** 5U19AI062629-17
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** JUDITH A JAMES
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $463,182
- **Award type:** 5
- **Project period:** 2004-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927977

## Citation

> US National Institutes of Health, RePORTER application 9927977, Mechanisms of Humoral Immune Protection Induced by Anthrax Vaccine Adsorbed (5U19AI062629-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9927977. Licensed CC0.

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