A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old

Abstract

This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were tittered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose.

Questions regarding the safety and duration of immunity following live yellow fever vaccination

“…Similar results were found in an earlier study in which 71% of subjects seroconverted after two MVA immunizations but only 28.8% maintained neutralizing antibody responses by 2 months after booster vaccination [53]. In contrast to these viruses, in which the difference in host-pathogen interactions are clearly due to differences in vaccine strain attenuation, the vaccine strains of YFV-17D are genetically stable viruses [54] and show similar safety and immunogenicity profiles [2,4–6]. It is therefore unlikely that the long-lived immunity or short-lived immunity observed among different vaccinated individuals (Figure 2) is due to differences in vaccine virus strains.…”

“…Importantly, seroconversion rates are also lower among children after YFV-17D vaccination (88% within 1–2 months after primary YFV-17D vaccination; [11]). A large clinical trial involving 1,966 children comparing 17D-213/77 and 17DD vaccines found seroconversion rates of only 84.8% and 85.8%, respectively [4]. However, among children aged 12 months or older, the seroconversion rate was only 69% when concomitant vaccination with measles, mumps, and rubella (MMR) was performed [4].…”

“…A large clinical trial involving 1,966 children comparing 17D-213/77 and 17DD vaccines found seroconversion rates of only 84.8% and 85.8%, respectively [4]. However, among children aged 12 months or older, the seroconversion rate was only 69% when concomitant vaccination with measles, mumps, and rubella (MMR) was performed [4]. These results are supported by prior studies in which only 552/792 children (70%) seroconvert after YFV vaccination when administered with MMR vaccination [6].…”

“…The live, attenuated YFV-17D vaccine was developed in 1936 and although there are two main substrains that are used in commercial manufacturing (17D and 17DD), there appear to be no major differences in safety or immunogenicity between YFV-17D vaccines [2,4–6]. Yellow fever vaccination is recommended for people living in endemic areas and for travelers who may visit endemic areas with the notable exception of infants <9 months of age and people with HIV, thymus disease, or other immunodeficiencies, since these represent vulnerable populations in which yellow fever vaccination is contraindicated [7].…”

A Meta-Analysis of Serological Response Associated with Yellow Fever Vaccination

“…Previous evidence suggested weaker immune response in specific groups, such as human immunodeficiency virus–infected people or infants 4. Specifically, vaccine efficacy in infants and children when coadministered with vaccination against measles, mumps, and rubella, has been recently questioned 20. These questions deserve further research effort.…”