Safety evaluation of adenovirus type 4 and type 7 vaccine live, oral in military recruits

Abstract

Before the widespread adoption of vaccination, adenovirus type 4 and type 7 were long associated with respiratory illnesses among military recruits. When supplies were depleted and vaccination was suspended in 1999 for approximately a decade, respiratory illnesses due to adenovirus infections resurged. In March 2011, a new live, oral adenovirus vaccine was licensed by the US Food and Drug Administration and was first universally administered to military recruits in October 2011, leading to rapid, dramatic elimination of the disease within a few months. As part of licensure, a postmarketing study (Sentinel Surveillance Plan) was performed to detect potential safety signals within 42days after immunization of military recruits. This study retrospectively evaluated possible adverse events related to vaccination using data from the Armed Forces Health Surveillance Branch Defense Medical Surveillance System (DMSS) database. Among 100,000 recruits who received the adenovirus vaccine, no statistically significant greater risk of prespecified medical events was observed within 42days after vaccination when compared with a historical cohort of 100,000 unvaccinated recruits. In an initial statistical analysis of International Classification of Disease, 9th Revision, Clinical Modification codes, a statistically significant higher risk for 19 other (not prespecified) medical events occurring in 5 or more recruits was observed among vaccinated compared with unvaccinated groups. After case record data abstraction for attribution and validation, two events (psoriasis [21 vs 7 cases] and serum reactions [12 vs 4 cases]) occurred more frequently in the vaccinated cohort. A causal relation of these rare events with adenovirus vaccination could not be established given confounding factors in the DMSS, such as coadministration of other vaccines and incomplete or inaccurate medical information, for some recruits. Prospective surveillance assessing these uncommon, but potentially relevant, immune-related symptoms may be beneficial in defining potential causal association with adenovirus vaccination.

Potential of live pathogen vaccines for defeating the COVID‐19 pandemic: History and mechanism

“…12 Therefore, the bivalent LPV containing types 4 and 7 replaced the previous LPV only containing type 4 adenovirus. 12,13,15 Routine vaccination with the bivalent LPV in US recruits began in 1971, and rates of adenovirus-associated ARD were reduced by up to 96%. 13 Despite their efficacy, the LPV vaccination was suspended in 1999 due to commercial reasons, and adenovirus-associated ARD in military recruits resurged.…”

Single-cycle adenovirus vectors in the current vaccine landscape

“…Unlike VSV and CMV, “Wild" fully replication-competent Ads have been used as vaccines against respiratory adenovirus infections in nearly a half million military recruits (34). Safety monitoring of 100,000 recruits that received RC-Ad showed no significant greater risk of specified medical events within 6 weeks of vaccination (34).…”

“…Safety monitoring of 100,000 recruits that received RC-Ad showed no significant greater risk of specified medical events within 6 weeks of vaccination (34). Psoriasis and serum reactions occurred more frequently in the vaccinated group (psoriasis occurred in 21 vs 7 vaccinated vs. control cases and serum reactions in 12 vs 4 vaccinated vs. control cases), but a causal relation of these rare events could not be established (34). …”

A Review of Possible Triggering or Therapeutic Effects of Antimicrobial Vaccines on Psoriasis

“…In a retrospective study, which evaluated the possible side effects related to adenovirus types 4 and 7 in military recruits, psoriasis (21 versus 7 cases) was found more frequently (RR = 2.44, 95% CI = 1.13-5.31) in the vaccinated group (n = 100,000) when compared to unvaccinated group (n = 100,000) [43].…”