Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation

Kim, Eun; Erdos, Geza; Huang, Shaohua; Kenniston, Thomas; Falo, Louis D.; Gambotto, Andrea

In this study, we describe the construction and immunological evaluation of two ZIKV vaccine candidates. Our initial evaluations indicated that the ZIKV vaccines Ad5.ZIKV-Efl and MNA-ZIKV-rEfl elicited a humoral immune response in immunized C57BL/6 mice. The humoral a c *** *** b *** n.s. *** * *** Fig. 2 . Characterization of ZIKV-specific immune responses induced by Ad5.ZIKV-Efl and MNA-ZIKV-rEfl. (a) Experimental schedule representing the immunization timeline. C57BL/6 mice (n = 5/group) were immunized subcutaneously with 1 × 10 11 viral particles of Ad.ZIKV-Efl or PBS as a negative control and boosted intranasally with the same amount of adenovirus two weeks later. MNA-ZIKV-rEfl was administered through intradermal delivery. (b) ZIKV-specific IgG antibody levels were measured at the indicated time points using ELISA. (c) The ZIKVneutralizing titers at week 6 post-immunization were measured using Vero cells by determining the reciprocal of the highest serum dilution still giving a 50% reduction in plaque number by 50% (PRNT 50 ), relative to samples incubated with pre-immunized control pooled sera. Statically significant differences (Tukey's test) are marked by bars and asterisks. *, P b 0.05; ***, P b 0.001. The same mean of neutralization was detected in two independent neutralizing tests with combined mouse sera. response was characterized by high titers of antibodies to E antigen as confirmed by ELISA, as well as neutralizing titers confirmed by PRNT 50 assay. Importantly, in pups born to immunized dams, ZIKV-specific immunity was passively transferred and protected them from day 7 challenge of 10 5 pfu of the ZIKV DAKAR41542 strain. The Ad5.ZIKV-Efl and MNA-ZIKV-rEfl vaccines were engineered using the 2015 Brazil ZIKV strain BeH815744. The BeH815744 strain E protein differs from the DAKAR41542 strain E protein used for challenge in three amino acids (98% identity). In general, the ZIKV envelope protein is highly conserved.