Short‐term reactogenicity and gender effect of anthrax vaccine: analysis of a 1967–1972 study and review of the 1955–2005 medical literature

Abstract

SUMMARYPurpose In the 1960s, the Centers for Disease Control and Prevention (CDC) held the investigational new drug (IND) application for the anthrax vaccine and collected short-term safety data from approximately 16 000 doses administered to almost 7000 individuals. While some recent anthrax vaccine safety studies have suggested that women experience more injection site reactions (ISRs), to our knowledge the IND safety data were not previously examined for a gender-specific difference. Methods We identified and analyzed a subset of the IND study data representing a total of 1749 persons who received 3592 doses from 1967 to 1972. Original data collection forms were located and information extracted, including: vaccine recipient's name, age at vaccination, gender, dose number, date of vaccination, lot number, grading of ISR, presence and type of systemic reactions. Overall and gender-specific rates for adverse reactions to anthrax vaccine were calculated and we performed a multivariable analysis. Results We found an ISR was associated with 28% of anthrax vaccine doses; however, 87% of these were considered mild. Systemic reactions were uncommon (<1%) and most (70%) accompanied an ISR. Our dose-specific analysis by gender found women had at least twice the risk of having a vaccine reaction compared to men. Our age-adjusted relative risk for ISR in women compared to men was 2.78 (95%CI: 2.29, 3.38). Conclusions Our results for both overall and gender-specific reactogenicity are consistent with other anthrax safety studies. To date, possible implications of these gender differences observed for anthrax and other vaccines are unknown and deserve further study.

Killed but Metabolically Active Bacillus anthracis Vaccines Induce Broad and Protective Immunity against Anthrax

“…To date, the only vaccine li- censed for human use in the United States is AVA, which is composed of B. anthracis culture filtrate from a toxinogenic strain that is adsorbed to aluminum hydroxide as an adjuvant. While AVA is a potent stimulator of toxin-neutralizing immunity, it is poorly characterized and frequently reactogenic (38,50). Additionally, the results from the first clinical trial with rPA102 demonstrated that it has a higher rate of systemic reactogenicity than AVA (19).…”

“…These data provided strong evidence that vaccination with KBMA B. anthracis vaccines induced a humoral response of substantially greater breadth than that elicited by rPA-based vaccines. vaccinees, while systemic and severe reactions occur at lower rates (1 to 4%) (38,50). The rPA102 vaccine is injected i.m., and when these vaccines were directly compared, significantly fewer adverse events were reported with rPA102 than with AVA (19).…”

Countering Anthrax: Vaccines and Immunoglobulins

“…Of interest, a retrospective analysis by the CDC of prelicensing data has shown that the sex differential also occurred in the 1960s, although it was unrecognized at that time [42]. More recently, analyses of meningococcal vaccinees, tetanus-diphtheria-pertussis vaccinees, and other vaccinees have shown similar sex differentials.…”

“…For decades, the vaccine's prescribing information cited systemic adverse event rates of 0.2%, based on CDC data [15,42]. Investigators and clinicians reporting from occupational health clinics likely tended to omit mild, self-limited events.…”

Anthrax vaccination strategies

“…As the target population grew, so too did concerns over the efficacy, cumbersome regimen (6 shots over 18 months and an annual booster), and possible side effects of the AVA vaccine (Pittman et al, 2001; Swanson-Biearman and Krenzelok, 2001; Geier and Geier, 2002; Greidanus and Honl, 2002; Hoffman et al, 2003; Lange et al, 2003; Wasserman et al, 2003; Geier and Geier, 2004; Hunter et al, 2004; Pittman et al, 2004; Grabenstein et al, 2006; Vasudev and Zacharisen, 2006; McNeil et al, 2007; Payne et al, 2007; Smith et al, 2007). Much energy has been devoted to investigating and addressing these concerns (Friedlander et al, 1999; Joellenbeck et al, 2002; Niu et al, 2009).…”