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Open AccessArticle

A Chimeric Zika Virus between Viral Strains MR766 and BeH819015 Highlights a Role for E-glycan Loop in Antibody-mediated Virus Neutralization

1
Université de La Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, Unité Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, 97491 Sainte-Clotilde, La Réunion, France
2
Plateforme CECEMA, Université de Montpellier, 34095 Montpellier, France
*
Author to whom correspondence should be addressed.
The authors have equally contributed to this work.
Vaccines 2019, 7(2), 55; https://doi.org/10.3390/vaccines7020055
Received: 28 May 2019 / Revised: 15 June 2019 / Accepted: 20 June 2019 / Published: 24 June 2019
(This article belongs to the Special Issue Current Flavivirus Research Important for Vaccine Development )
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. View Full-Text
Keywords: arbovirus; Zika virus; viral clone; chimeric virus; vaccine; immunity; mouse model; humoral response; viral envelope protein; neutralizing antibody arbovirus; Zika virus; viral clone; chimeric virus; vaccine; immunity; mouse model; humoral response; viral envelope protein; neutralizing antibody
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Frumence, E.; Viranaicken, W.; Bos, S.; Alvarez-Martinez, M.-T.; Roche, M.; Arnaud, J.-D.; Gadea, G.; Desprès, P. A Chimeric Zika Virus between Viral Strains MR766 and BeH819015 Highlights a Role for E-glycan Loop in Antibody-mediated Virus Neutralization. Vaccines 2019, 7, 55.

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