Abstract
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus which is of major public health concern. ZIKV infection is recognized as the cause of congenital Zika disease and other neurological defects, with no specific prophylactic or therapeutic treatments. As the humoral immune response is an essential component of protective immunity, there is an urgent need for effective vaccines that confer protection against ZIKV infection. In the present study, we evaluate the immunogenicity of chimeric viral clone ZIKBeHMR-2, in which the region encoding the structural proteins of the African strain MR766 backbone was replaced with its counterpart from the epidemic strain BeH819015. Three amino-acid substitutions I152T, T156I, and H158Y were introduced in the glycan loop of the E protein (E-GL) making ZIKBeHMR-2 a non-glycosylated virus. Adult BALB/c mice inoculated intraperitoneally with ZIKBeHMR-2 developed anti-ZIKV antibodies directed against viral proteins E and NS1 and a booster dose increased antibody titers. Immunization with ZIKBeHMR-2 resulted in a rapid production of neutralizing anti-ZIKV antibodies. Antibody-mediated ZIKV neutralization was effective against viral strain MR766, whereas epidemic ZIKV strains were poorly sensitive to neutralization by anti-ZIKBeHMR-2 immune sera. From our data, we propose that the three E-GL residues at positions E-152, E-156, and E-158 greatly influence the accessibility of neutralizing antibody epitopes on ZIKV.
Highlights
Zika virus (ZIKV), belonging to the flavivirus genus of the Flaviviridae family, was first discovered in Africa in 1947 [1]
Viral clone ZIKBeHMR-1 is a chimeric ZIKV in which the structural protein region of molecular clone MR766MC was replaced with that of molecular clone BR15MC derived from epidemic Brazilian strain BeH819015 [16] (Figure 1)
We constructed a nonglycosylated viral clone ZIKBeHMR-2 which differs from ZIKBeHMR-1 by the three substitutions have been found into the MR766 E protein that is non-glycosylated
Summary
Zika virus (ZIKV), belonging to the flavivirus genus of the Flaviviridae family, was first discovered in Africa in 1947 [1]. Phylogenetic analysis distinguished African and Asian lineages of ZIKV [2,3]. ZIKV has been known to occur in sporadic outbreaks in Africa and South-Asia. ZIKV became a public health concern with epidemics occurring in Yap islands (2007), French Polynesia (2013) and South America (2015) [4,5]. ZIKV is recognized as the cause of congenital Zika syndrome leading to severe neurodevelopmental diseases and of other neurological complications such as Vaccines 2019, 7, 55; doi:10.3390/vaccines7020055 www.mdpi.com/journal/vaccines. Natural transmission of ZIKV in humans involves infectious mosquitoes from the Aedes genus, but ZIKV transmission has been documented through sexual contact, blood transfusion and intrauterine transmission [7]
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