Abstract
Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are major causative agents of hand, foot, and mouth diseases (HFMDs), and EV71 is now recognized as an emerging neurotropic virus in Asia. Effective medications and/or prophylactic vaccines against HFMD are not available. The current results from mouse immunogenicity studies using in-house standardized RD cell virus neutralization assays indicate that (1) VP1 peptide (residues 211–225) formulated with Freund's adjuvant (CFA/IFA) elicited low virus neutralizing antibody response (1/32 titer); (2) recombinant virus-like particles produced from baculovirus formulated with CFA/IFA could elicit good virus neutralization titer (1/160); (3) individual recombinant EV71 antigens (VP1, VP2, and VP3) formulated with CFA/IFA, only VP1 elicited antibody response with 1/128 virus neutralization titer; and (4) the formalin-inactivated EV71 formulated in alum elicited antibodies that cross-neutralized different EV71 genotypes (1/640), but failed to neutralize CVA16. In contrast, rabbits antisera could cross-neutralize strongly against different genotypes of EV71 but weakly against CVA16, with average titers 1/6400 and 1/32, respectively. The VP1 amino acid sequence dissimilarity between CVA16 and EV71 could partially explain why mouse antibodies failed to cross-neutralize CVA16. Therefore, the best formulation for producing cost-effective HFMD vaccine is a combination of formalin-inactivated EV71 and CAV16 virions.
Highlights
Hand, foot and mouth diseases (HFMDs) caused by enteroviruses like Coxsackievirus A16 (CVA16) and Enterovirus 71 (EV71) infections have become serious public health problems in Southeast Asia [1,2,3,4,5]
The current results from mouse immunogenicity studies using in-house standardized RD cell virus neutralization assays indicate that (1) VP1 peptide formulated with Freund’s adjuvant (CFA/incomplete Freund’s adjuvant (IFA)) elicited low virus neutralizing antibody response (1/32 titer); (2) recombinant virus-like particles produced from baculovirus formulated with complete Freund’s adjuvant (CFA)/IFA could elicit good virus neutralization titer (1/160); (3) individual recombinant EV71 antigens (VP1, VP2, and VP3) formulated with CFA/IFA, only VP1 elicited antibody response with 1/128 virus neutralization titer; and (4) the formalininactivated EV71 formulated in alum elicited antibodies that cross-neutralized different EV71 genotypes (1/640), but failed to neutralize coxsackievirus A16 (CVA16)
Since there are no standardized antigens or immuno assays to reveal the potency of vaccine candidates, it was difficult to compare which method of EV71 vaccine development elicited the most effective immune response
Summary
Foot and mouth diseases (HFMDs) caused by enteroviruses like Coxsackievirus A16 (CVA16) and Enterovirus 71 (EV71) infections have become serious public health problems in Southeast Asia [1,2,3,4,5]. Recent outbreaks of EV71 infections have led to fatalities and neurological complications in children, and the virus is recognized as an important emerging infectious disease [3,4,5]. Two structural proteins (VP1 and VP4) have been used for EV71 molecular genotyping and epidemiological monitoring. Based on the molecular epidemiological surveillance in Taiwan, CVA16 is the most common virus causing HFMD in children [12].
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