Evaluation of sex, race, body mass index and pre-vaccination serum progesterone levels and post-vaccination serum anti-anthrax protective immunoglobulin G on injection site adverse events following anthrax vaccine adsorbed (AVA) in the CDC AVA human clinical trial

• Authors: Tracy Pondo, Centers for Disease Control and Prevention; Charles E. Rose, Centers for Disease Control and Prevention; Stacey W. Martin, Centers for Disease Control and Prevention; Wendy A. Keitel, Baylor College of Medicine; Harry L Keyserling, Emory University; Janiine Babcock, Walter Reed Army Institute of Research; Scott Parker, University of Alabama Birmingham; Robert M. Jacobson, Mayo Clinic; Gregory A. Poland, Mayo Clinic; Michael M McNeil, Centers for Disease Control and Prevention
• Journal Title: Vaccine
• Volume: Volume 32, Number 28
• Publisher: Elsevier | 2014-06-12, Pages 3548-3554
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.vaccine.2014.04.025
• Subjects: Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Medicine, Research & Experimental; Research & Experimental Medicine; Anthrax vaccine adsorbed; Anthrax vaccines/adverse events; Sex factors; Race; Body mass index; Immunological response; IMMUNE-RESPONSES; RANDOMIZED-TRIAL; SAFETY PROFILE; IMMUNOGENICITY; DISABILITY; IMMUNIZATION; PREGNANCY; HORMONES; GENDER; SYSTEM

Abstract

Background: Anthrax vaccine adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. Methods: We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial's vaccinated cohort (n= 1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n= 227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Results: Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Conclusions: Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants.