November 10, 2021Human Vaccines & ImmunotherapeuticsOpen Access

Evaluation of the cross-neutralization activities elicited by Coxsackievirus A10 vaccine strains

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Why the study?

Increasing disease severity and circulating mutants and recombinants of Coxsackievirus A10 raised public health concern, creating a need for a vaccine with broad-spectrum and homogenous protective capacity.

Structured PICO

Population

30 samples of plasma collected from naturally infected human adults in mainland China, 18 sera samples from murine immunized with 18 CV-A10 strains, and 1-day-old BALB/c mice for in vivo challenge.

Intervention

Anti-S102 serum (and other anti-CV-A10 sera) administered via intraperitoneal route.

Comparator

Diluents (negative controls).

Outcome

Cross-neutralization activity in vitro and survival after lethal challenge with CV-A10 strains in vivo at 21 days.surrogate

Anti-S102 serum exhibited broad-spectrum cross-protective effects against multiple CV-A10 strains in vivo, providing a framework for CV-A10 vaccine development.

Implication

Strain-specific cross-neutralization patterns guide CV-A10 vaccine strain selection; leaves open clinical translation in humans.

Abstract

Increased severity of diseases caused by Coxsackievirus A10 (CV-A10) as well as a large number of mutants and recombinants circulating in the population are a cause of concern for public health. A vaccine with broad-spectrum and homogenous protective capacity is needed to prevent outbreaks of CV-A10. Here, we evaluated cross-neutralization of prototype strain and 17 CV-A10 strains from related manufacturers in mainland China in vitro using 30 samples of plasma collected from naturally infected human adults and 18 sera samples from murine immunized with the above strains of CV-A10. Both human plasma and murine sera exhibited varying degrees of cross-neutralizing activities. Prototype A/Kowalik and sub-genotype C3/S113 were most difficult to neutralize. Among all strains tested, neutralization of S102 and S108 strains by 18 different sera was the most uniform, suggesting their suitability for detection of NtAb titers of different vaccines for avoiding biases introduced by detection strain. Furthermore, among all immune-sera, cross-neutralization of the 18 strains of CV-A10 by anti-S110 and anti-S102 was the most homogenous. Anti-S102 exhibiting higher geometric mean titer (GMT) in vitro was evaluated for its cross-protection capacity in vivo. Remarkably, administration of anti-S102 protected mice from lethal dosage of eight strains of CV-A10. These results provide a framework for formulating strategies for the R&D of vaccines targeting CV-A10 infections.