Yellow Fever 17D Vaccine Safety and Immunogenicity in the Elderly

Abstract

The incidence of serious and severe multisystem adverse events (AEs) following yellow fever (YF) 17D vaccine is higher in persons of advanced age. One hypothesis for the occurrence of these AEs in the elderly is immunological senescence and a reduced ability to clear the vaccine virus infection. We determined age-specific rates of serious and nonserious AEs in two large clinical trials of two YF 17D vaccines from different manufacturers. In addition, we analyzed AEs reported in a large general practice data base in the United Kingdom. Neutralizing antibody responses were compared in young and elderly subjects. In the clinical trials, involving a total of 4,532 subjects, there were no neurological and viscerotropic AEs; interestingly, the incidence of common injection site and systemic AEs was significantly lower in elderly than in younger subjects. The neutralizing antibody categorical and quantitative responses were equivalent across younger and elderly subjects. In contrast, the larger retrospective analysis of 43,555 persons receiving YF 17D in the UK general practice database revealed a higher incidence of significant neurologic and multisystem AEs with advancing age. The age-specific reporting rate ratio (RRR) was approximately twice that in the 25-44 year-old reference group for subjects in the 45-64 year age group (RRR 1.82; 95% CI 0.88,3.77) and 3-fold higher for the 65-74 year-old age group (RRR 2.82; 95% CI 0.81, 9.81). These results are consistent with previous reports on YF vaccine safety in the US (Martin M, et al. Emerg Infect Dis 2001;6:945-51; Khromova et al., Vaccine 2005;23:3256-63). In elderly persons, YF 17D vaccine is associated with a higher frequency of significant AEs in the elderly but a lower incidence of common nonserious side-effects. The neutralizing antibody response, which is the mediator of protective immunity to YF, is not diminished in healthy, elderly persons.

Vacinação contra febre amarela em pacientes com diagnósticos de doenças reumáticas, em uso de imunossupressores

“…Dentro de 30 dias, mais de 90% dos vacinados desenvolvem anticorpos contra a febre amarela 23 . Aproximadamente, 100% dos indivíduos tornam-se imunizados 17 .…”

“…No Brasil, ocorreram 4 casos (idade de 4 a 22 anos) e todos morreram entre 4 a 6 dias de doença 22 . Nos Estados Unidos, a incidência de efeitos sistêmicos graves é maior em indivíduos maiores de 60 anos 17 .…”

“…Também, podem ser devido a reações de hipersensibilidade como exantema, urticária, febre, anafilaxia, asma ou angioedema 17 . Esses efeitos costumam ocorrer entre 5 e 7 dias da vacinação, período em que ocorre uma viremia transitória 10 11 .…”

The phylogeny of yellow fever virus 17D vaccines

“…Up to now no link could be established between the occurrence of SAEs and YFvaccine genotypes. Indication exists that certain genetic predispositions of the vaccinees trigger the symptoms [19,20]. Age is considered as risk factor.…”

Safety and tolerability of yellow fever vaccines

“…Persons above the age of 60 may be at a higher risk of side-effects following vaccination. 17,22,24,25 • Thymectomy and thymus disease: Thymectomy and thymus disease are a contraindication for vaccination, as they increase the risk of YEL-AVD. Review: Safety and tolerability of yellow fever vaccines…”