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Long-term immunity against yellow fever in children vaccinated during infancy: a longitudinal cohort study
Cristina Domingo1, Juliane Fraissinet1, Patrick O Ansah2
1Robert Koch Institute, Highly Pathogenic Viruses (ZBS 1), Centre for Biological Threats and Special Pathogens, WHO Collaborating Centre for Emerging Infections and Biological Threats, Berlin, Germany.
Insights
Yellow fever vaccine immunity wanes rapidly in infants vaccinated at 9 months, suggesting a single dose may not provide lifelong protection. Booster vaccinations are likely needed to maintain herd immunity and prevent outbreaks in endemic areas.
Area of Science:
- Immunology
- Vaccinology
- Public Health
Background:
- Routine infant vaccination against yellow fever uses a single dose administered at 9-12 months.
- Long-term immunity following infant yellow fever vaccination is not well-established.
- The Expanded Programme on Immunization (EPI) relies on this vaccination strategy.
Purpose of the Study:
- To evaluate the long-term persistence of neutralizing antibodies to yellow fever virus after routine infant vaccination.
- To assess the duration of protective immunity in children vaccinated at approximately 9 months of age.
Main Methods:
- Longitudinal cohort study involving Malian and Ghanaian children vaccinated against yellow fever.
- Microneutralisation assay used to measure yellow fever virus-specific antibodies.
- Follow-up periods of up to 6 years post-vaccination, with exclusion of revaccinated or baseline seropositive individuals.
Main Results:
- Seropositivity rates significantly decreased from 28 days post-vaccination to 4.5 years in Mali (96.7% to 50.4%) and 2.3 years in Ghana (72.7% to 27.8%).
- At 6 years post-vaccination, seropositivity in Ghanaian children was 43.1%, potentially confounded by unrecorded events.
- Antibody concentrations were standardized against the WHO International Standard for yellow fever.
Conclusions:
- Rapid waning of yellow fever immunity in infants vaccinated at 9 months suggests the single-dose recommendation may require revision.
- Booster vaccinations might be necessary to achieve and maintain the 80% population immunity threshold required to prevent yellow fever outbreaks.
- Findings highlight the need for further research into optimal yellow fever vaccination schedules in endemic regions.
Background:
A single dose of vaccine against yellow fever is routinely administered to infants aged 9-12 months under the Expanded Programme on Immunization, but the long-term outcome of vaccination in this age group is unknown. We aimed to evaluate the long-term persistence of neutralising antibodies to yellow fever virus following routine vaccination in infancy.
Methods:
We did a longitudinal cohort study, using a microneutralisation assay to measure protective antibodies against yellow fever in Malian and Ghanaian children vaccinated around age 9 months and followed up for 4·5 years (Mali), or 2·3 and 6·0 years (Ghana). Healthy children with available day-0 sera, a complete follow-up history, and no record of yellow fever revaccination were included; children seropositive for yellow fever at baseline were excluded. We standardised antibody concentrations with reference to the yellow fever WHO International Standard.
Findings:
We included 587 Malian and 436 Ghanaian children vaccinated between June 5, 2009, and Dec 26, 2012. In the Malian group, 296 (50·4%, 95% CI 46·4-54·5) were seropositive (antibody concentration ≥0·5 IU/mL) 4·5 years after vaccination. Among the Ghanaian children, 121 (27·8%, 23·5-32·0) were seropositive after 2·3 years. These results show a large decrease from the proportions of seropositive infants 28 days after vaccination, 96·7% in Mali and 72·7% in Ghana, reported by a previous study of both study populations. The number of seropositive children increased to 188 (43·1%, 95% CI 38·5-47·8) in the Ghanaian group 6·0 years after vaccination, but this result might be confounded by unrecorded revaccination or natural infection with wild yellow fever virus during a 2011-12 outbreak in northern Ghana.
Interpretation:
Rapid 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.
Funding:
Wellcome Trust.
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