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

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.

Adverse events and association with age, sex and immunological parameters of Q fever vaccination in patients at risk for chronic Q fever in the Netherlands 2011

“…Here, proportions of reported AE were consistently higher in women than in men, both for milder and more pronounced AE. Few publications about AE differentiate between sexes and age [37][38][39]. Yet, we have noted such differences in several vaccination programmes for adults and children, depending on age and type of event [40].…”

Immunogenicity and safety of human papillomavirus (HPV) vaccination in Asian populations from six countries: a meta-analysis

“…Therefore, specific information on HPV vaccine immunogenicity and safety profiles in Asian populations is scarcely available. Extrapolation of results of vaccine trials from western to Asian countries is questionable since trials outcome, for example vaccine efficacy, might be different as it possibly caused by several variables, including race as well as social and behavioral factors (23,24). Therefore, it is important to obtain specific estimations of the characteristics of HPV vaccination in Asian populations, especially with respect to immunogenicity, efficacy and safety.…”

Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination

“…Following vaccination, females were three times more likely to develop swelling, pain, and activity limitations than men. Interestingly, individuals of African American descent were significantly less likely to report an AE than nonAfrican Americans (14). To assess the influence of sex or other demographic factors on the prevalence of AEs in this real-world cohort of AVA vaccinees, we determined the relative ratios of total AEs (both LLRs and SRs) occurring in multiple demographic groups.…”

“…In many animal models, the magnitude and toxin neutralization ability of the humoral response to PA is correlated with protection against B. anthracis spore challenge (8)(9)(10)(11)(12). Since AVA became mandatory for select populations in 1998, concerns have arisen regarding the relatively high rate of adverse events (AEs), especially in women (13,14). Among AVA vaccinees, 0.5 to 1% report systemic AEs and 4 to 10% report local AEs to health care professionals (13,15), similar to other adult vaccinations (15)(16)(17).…”

“…In AVA vaccination specifically, intramuscular rather than subcutaneous administration may reduce the rate of local AEs but does not seem to influence the rate of systemic AEs (20). Additionally, certain types of reactions may be associated with sex, ethnicity, and body mass index (14,16,17). Despite the results of these studies, little is known about the measurable correlates or immune mechanisms that may underlie adverse events in response to AVA.…”