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.
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.
Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States. Electronic address: dio2@cdc.gov.
Tracy
T
Pondo
Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.
Charles E
CE
Rose
Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.
Stacey W
SW
Martin
Baylor College of Medicine, Houston, TX, United States.
Wendy A
WA
Keitel
Emory University School of Medicine, Atlanta, GA, United States.
Harry L
HL
Keyserling
Walter Reed Army Institute of Research, Washington, DC, United States.
Janiine
J
Babcock
University of Alabama at Birmingham, Birmingham, AL, United States.
Scott
S
Parker
Mayo Clinic, Rochester, MN, United States.
Robert M
RM
Jacobson
Mayo Clinic, Rochester, MN, United States.
Gregory A
GA
Poland
Immunization Safety Office, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States.
Michael M
MM
McNeil
D000328:Adult; D000881:Anthrax / Q000517:prevention & control; D022122:Anthrax Vaccines / Q000009:adverse effects*; D000907:Antibodies, Bacterial / Q000097:blood*; D015992:Body Mass Index; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011374:Progesterone / Q000097:blood*; D044469:Racial Groups; D012737:Sex Factors
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D011374:Progesterone
Anthrax vaccine adsorbed; Anthrax vaccines/adverse events; Body mass index; Immunological response; Race; Sex factors