Journal Article

Sex difference in immune response to vaccination: A participant-level meta-analysis of randomized trials of IMVAMUNE® smallpox vaccine

Ewell, Marian G., Troy, Jesse D., Frey, Sharon E., Hill, Heather R.

2015

Overview

•We studied sex differences in response to IMVAMUNE® using meta-analysis.•We analyzed study-specific estimates and patient-level data from randomized trials.•Men had consistently higher ELISA titers than women over time.•The geometric mean peak titer in men was 27% higher than women.•Sex should be considered in future testing of IMVAMUNE and other MVA-based vaccines. Previous research shows immune response to vaccination differs by sex but this has not been explored for IMVAMUNE®, a replication-deficient smallpox vaccine developed in response to the potential for bioterrorism using smallpox. We conducted a participant-level meta-analysis (N=275, 136 men, 139 women) of 3 randomized trials of IMVAMUNE conducted at 13 centers in the US through a federally-funded extramural research program. Studies were eligible for inclusion if they tested the standard dose (1×108TCID50/mL on Days 0 and 28) of liquid formulation IMVAMUNE, were completed at the time of our search, and enrolled healthy vaccinia-naïve participants. Models of the peak log2 ELISA and PRNT titers post-second vaccination were constructed for each study with sex as a covariate. Results from these models were combined into random effects meta-analyses of the sex difference in response to IMVAMUNE. We then compared this approach with fixed effects models using the combined participant level data. In each study the mean peak log2 ELISA titer was higher in men than women but no single study demonstrated a statistically significant difference. Combination of the adjusted study-specific estimates into the random effects model showed a higher mean peak log2-titer in men compared with women (absolute difference [men–women]: 0.32, 95% CI: 0.02–0.60). Fixed effects models controlling for study showed a similar result (log2 ELISA titer, men–women: 0.34, 95% CI: 0.04–0.63). This equates to a geometric mean peak titer that is approximately 27% higher in men than women (95% CI: 3–55%). Peak log2 PRNT titers were also higher (although not significantly) in men (men–women: 0.14, 95% CI: −0.30 to 0.58). Our results show statistically significant differences in response to IMVAMUNE comparing healthy, vaccinia-naïve men with women and suggest that sex should be considered in further development and deployment of IMVAMUNE and other MVA-based vaccines.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Allergy and Immunology / Antibodies, Viral - blood / Antibodies, Viral - immunology / Bioterrorism / Clinical trials / Enzyme-Linked Immunosorbent Assay / Female / Gender differences / geometry / Health care / Humans / Immune response / Immune system / Immunity / Imvamune / Infectious diseases / Male / Men / Meta-analysis / MVA vaccine / Pathogens / Population / Randomization / Randomized Controlled Trials as Topic / research programs / Sex / Sex Factors / Smallpox / Smallpox - prevention & control / Smallpox Vaccine - immunology / Statistical analysis / Statistical significance / United States / Vaccination / Vaccines / Vaccinia / Vaccinia virus / Variola virus / women / Womens health