Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints

Zhu, Wenbo; Jin, Pengfei; Li, Jingxin; Zhu, Fengcai; Liu, Pei

doi:10.1080/14760584.2017.1335603

Cited by 15 publications

(4 citation statements)

References 13 publications

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“…Nonetheless, it is important to evaluate the vaccine in different populations especially in countries where other EV-A71 genotypes are circulating.The neutralization titres were significantly higher in vaccine groups compared with placebo groups, and recipients of all the three vaccines demonstrated high geometric mean titres up to 2 years later.A neutralization titre of >1:16 is suggestive of cross-protection against other genotypes,175 and a titre of >1:42 has been recently been proposed as a correlate of long-term protection 182. However, all three vaccines do not offer cross-protection against other enteroviruses [173][174][175]177,178.…”

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confidence: 99%

Immune responses against enterovirus A71 infection: Implications for vaccine success

Aw-Yong

NikNadia

Tan

et al. 2019

Reviews in Medical Virology

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Summary Enterovirus A71 (EV‐A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV‐A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV‐A71 infection is very common. Children of very young age are particularly vulnerable. Large‐scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B‐ and T‐cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T‐cell epitopes that induce cross‐reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL‐6, IL‐10, IL‐17A, MCP‐1, IL‐8, MIG, IP‐10, IFN‐γ, and G‐CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV‐A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV‐A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross‐protection and memory T‐cell responses among enteroviruses.

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confidence: 99%

Immune responses against enterovirus A71 infection: Implications for vaccine success

Aw-Yong

NikNadia

Tan

et al. 2019

Reviews in Medical Virology

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“…Zhu and colleagues suggested that long-term protection is afforded when a standardized IU is no less than 70.2IU/ml. [22] Using this criterion, 98.96%, 99.17%, and 99.79% subjects in our study may have long-term protection from EV-A71 related diseases, regardless of which vaccine is used.…”

Section: Discussionmentioning

confidence: 81%

Immunogenicity and safety of inactivated enterovirus A71 vaccines in children aged 6-35 months in China: a non-inferiority, randomised controlled trial

Gao

Wang

et al. 2021

The Lancet Regional Health - Western Pacific

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Summary Background China's three inactivated enterovirus A71 (EV-A71) vaccines are the first and currently world's only EV-A71 vaccines approved by a national regulatory authority and used to prevent EV-A71 associated diseases. The three vaccines vary by vaccine strain, manufacturing cell substrate, and antigen dose, but no head-to-head comparisons of these vaccines have been done. We compared immunogenicity of the vaccines in children 6-35 months old. Methods We recruited healthy children aged 6-35 months who lived in a study site county into a multicentre, open-label, non-inferiority, three-group, randomised controlled trial that was conducted in five counties in China. Enrolled children were randomly assigned (1:1:1) to receive two doses of one of the three EV-A71 vaccines. The primary outcome was the proportion of children with EV-A71 neutralizing antibody seroconversion 4 weeks after the second dose; a secondary outcome was adverse events in the 4 weeks after each dose. Analyses of immunogenicity included all children who completed the study (per-protocol analysis). Safety analysis included all children completed safety follow-up after at least one. We used a 10% margin to establish non-inferiority. This trial was registered on a World Health Organization platform: Chinese Clinical Trial Registry (ChiCTR1900026663). Findings 1631 children were assessed for eligibility between Nov 4 and Nov 20, 2019. Of 1500 (92%) enrolled children, 500 were assigned to vaccine group A, B, or C; 483 in group A,484 in group B, and 487 in group C completed the study. Before dose one, the seropositive rates in groups A, B, and C were 9.7%, 7.2%, and 7.0%. Four weeks after the second dose, seroconversion rates of groups A, B, and C were 98.8%, 99.4% and 99.8% - mutually non-inferior in all two-group comparisons. There were no serious adverse events in any group and no evidence of a difference among the three groups in the incidence of local adverse event or systemic adverse event. Fever was the most common adverse event. All children with reported adverse events recovered. Interpretation Non-inferior and high seroconversion rates and equivalent safety of three EV-A71 vaccines supports use any of these vaccines to prevent EV-A71-associated diseases. These results may be useful for regulators, vaccine policy makers, and immunization programmes in China and in countries where EV-A71 is endemic.

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“…Previous studies showed that the C-EV71 vaccine had conveyed good immunogenicity in children aged 36-71 months in phase III and IV clinical trials. 24,25 Additionally, the B-EV71 vaccine in children aged 36-71 months was also non-inferior to that in children aged 6-35 months. The anti-EV71 neutralising antibody of children aged 6-35 months in this study was similar to that reported in the lot-to-lot consistency study after the B-EV71 vaccine was available on the market.…”

Section: Discussionmentioning

confidence: 97%

Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial

Tong¹,

Zhang²,

Chen³

et al. 2022

eClinicalMedicine

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Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints

Abstract: NCT01508247.

Cited by 15 publications

References 13 publications

Immune responses against enterovirus A71 infection: Implications for vaccine success

Immune responses against enterovirus A71 infection: Implications for vaccine success

Immunogenicity and safety of inactivated enterovirus A71 vaccines in children aged 6-35 months in China: a non-inferiority, randomised controlled trial

Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial

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