Are booster doses of yellow fever vaccine needed?
Authors: Pedro F C Vasconcelos, Alan D T Barrett
Journal: The Lancet Infectious Diseases (2019)

Yellow fever is a major public health problem. A live attenuated vaccine, developed by Max Theiler and colleagues in the 1930s,1Theiler M Smith HH Use of yellow fever modified by in vitro cultivation for human immunization.J Exper Med. 1937; 65: 787-800Crossref PubMed Scopus (262) Google Scholar has helped to control yellow fever, but the duration of protective immunity has been questioned. In The Lancet Infectious Diseases, Cristina Domingo and colleagues2Domingo C Fraissinet J Ansah PO et al.Long-term immunity against yellow fever in children vaccinated during infancy: a longitudinal observational study.Lancet Infect Dis. 2019; (published online Sept 19)https://doi.org/10.1016/S1473-3099(19)30323-8PubMed Scopus (20) Google Scholar report on the duration of immunity in infants vaccinated at 9 months of age. This study has practical importance, because 9 months is the recommended age at which to administer the vaccine as part of the Expanded Program of Immunization in endemic countries. Domingo and colleagues2Domingo C Fraissinet J Ansah PO et al.Long-term immunity against yellow fever in children vaccinated during infancy: a longitudinal observational study.Lancet Infect Dis. 2019; (published online Sept 19)https://doi.org/10.1016/S1473-3099(19)30323-8PubMed Scopus (20) Google Scholar studied two cohorts, one in Ghana and the other in Mali, and showed waning immunity less than 6 years after vaccination in both, which is quicker than reported in some adult studies. Despite high concentrations of seroprotective neutralising antibodies within 3 months of vaccination in around 98% of vaccinees, serum neutralisation titres decline over time,3Lindsey NP Horichi KA Fulton C et al.Persistence of yellow fever virus-specific neutralizing antibodies after vaccination among US travelers.J Trav Med. 2018; 25: 1-6Crossref Scopus (35) Google Scholar so booster doses were given every 10 years. In 2013, WHO recommended that the 10-year boosters be abandoned, except for special populations. This recommendation was endorsed by the WHO Strategic Advisory Group of Experts on Immunization, and a WHO position paper was published.4WHOVaccines and vaccination against yellow fever: WHO position paper, June 2013—recommendations.Vaccine. 2014; 33: 76-77Crossref PubMed Scopus (47) Google Scholar This position paper recognised that few data on the immunisation of infants existed. Domingo and colleagues' study provides some information to fill this gap in knowledge and suggests that booster doses of vaccine are needed in this population. Similar indications have come from studies in adults,5Campi-Azevedo AC Teixeira-Carvalho A Antonelli LR et al.Booster dose after 10 years is required following 17DD-YF-primary vaccination.Hum Vaccin Immunother. 2016; 12: 491-502Crossref PubMed Scopus (38) Google Scholar, 6Costa-Pereira C Campi-Azevedo AC Coelho-Dos-Reis JG et al.Multi-parameter approach to evaluate the timing of memory status after 17DD-YF primary vaccination.PLoS Negl Trop Dis. 2018; 12e0006462Crossref PubMed Scopus (11) Google Scholar, 7Vasconcelos PFC Single shot of 17D vaccine may not confer life-long protection against yellow fever.Mem Inst Oswaldo Cruz. 2018; 113: 135-137Crossref PubMed Scopus (13) Google Scholar, 8Collaborative group for studies on yellow fever vaccinesDuration of immunity in recipients of two doses of 17DD yellow fever vaccine.Vaccine. 2019; 37: 5129-5135Crossref PubMed Scopus (9) Google Scholar especially in Brazil, with strong evidence that a booster dose is needed at 10 years to obtain long-term protection against yellow fever. These studies showed that yellow fever antibody concentrations decline considerably in both Brazilian children and adults after primary 17D vaccination and that boosters of vaccine should be used to protect travellers and inhabitants of endemic areas. Thus, Domingo and colleagues' study reinforces the need for additional information on the number of vaccine doses required for long-term protection of children, particularly because the two cohorts generated data that differed in significance. Of note, 50·4% (95% CI 46·4–54·5) of the Malian cohort were seropositive after 4·5 years, whereas 43·1% (38·5–47·8) of the Ghaniaian cohort was seropositive after 6·0 years. In a previously published study,9Chowdhury Roy Meier P C Laraway H et al.Immunogenicity of yellow fever vaccine coadministered with MenAfriVac in healthy infants in Ghana and Mali.Clin Infect Dis. 2015; 61: S586-S593Crossref PubMed Scopus (16) Google Scholar the Ghaniaian cohort had lower seropositivity than the Malian cohort 28 days after vaccination (72·7% vs 96·7%), suggesting fundamental differences between the two cohorts. Although Domingo and colleagues suggest that the WHO recommendations on vaccination be revisited, the differences between the Malian and Ghanaian cohorts indicate that other factors, which remain to be identified, are involved in the duration of immunity and seropositivity. Vaccines from different producers were used for the two cohorts, which presumably contain different quantities of vaccine virus and might stimulate the immune system differently. Additional research is needed for this group of vaccinees to determine whether different yellow fever vaccines stimulate the immune system differently. Equivalent studies will also be needed in some of the other 40 countries where yellow fever is endemic,10Monath TP Vasconcelos PFC Yellow fever.J Clin Virol. 2015; 64: 160-173Crossref PubMed Scopus (347) Google Scholar assessing all four WHO prequalified vaccines, to provide more information on whether booster doses are needed for children and, consequently, whether modifications to the current immunisation regimen are necessary. We declare no competing interests. Long-term immunity against yellow fever in children vaccinated during infancy: a longitudinal cohort studyRapid waning of immunity during the early years after vaccination of 9-month-old infants argues for a revision of the single-dose recommendation for this target population in endemic countries. The short duration of immunity in many vaccinees suggests that booster vaccination is necessary to meet the 80% population immunity threshold for prevention of yellow fever outbreaks. Full-Text PDF Open Access