Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation

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

To further understand how the vaccine induced ZIKV E-specific immunity, neutralizing the ZIKV in vivo and protecting the animal from its pathogenic effects, we developed a passive protection suckling mouse model. Building upon the knowledge (Dick et al., 1952 ) that day 7-(but not day 14-) old suckling mice are susceptible to ZIKV infection via the i.p. route showing neurological signs, pups were obtained by mating immunized female with nonimmunized male mice at week 3 after booster immunization. Pups were challenged i.p. at seven days after birth with 10 5 pfu of ZIKV DAKAR41542, monitored daily for mortality, and weighed for 15 days. The mean time to disease onset (10% weight loss) was slightly earlier in the pups from PBS-immunized mice than in those from MNA-ZIKV-rEfl-immunized mice, although the difference was not significant (7.75 vs. 8.25 days, P = 0.1598) ( Table 1 ). All pups born to PBS-immunized mice showed more than a 20% body weight loss in the 10 days postinfection. However, weight loss in the MNA-ZIKV-rEfl pups was reduced and a significant difference was found from day 12 (P b 0.01; P b 0.001, day 13-day 15) after challenge when compared to the PBS pups. No weight loss was observed in the pups born to the dams immunized with Ad5.ZIKV-Efl vaccine and no significant difference was measured between the pups of Ad5.ZIKV-Efl-immunized mice and the unchallenged control pups for the entire period. The significant difference started at day 8 (P b 0.01; P b 0.001, day 9-day 15) after challenge when compared to the PBS pups. (Fig. 3a) . The survival rates of pups from two animals in each group were also monitored after challenge with ZIKV DAKAR41542. Survival rates of 100% (10/10) and 50% (3/6) were observed in the pups from Ad5.ZIKV-Efl-and MNA-ZIKV-rEfl-immunized dams, respectively, whereas a 12.5% (1/8) survival rate was seen in pups from PBS-immunized dams (Fig. 3b) . The differences between the pups from Ad5.ZIKV-Efl-and those from PBS-immunized dams and between the pups from Ad5.ZIKV-Efl-and those from MNA-ZIKV-immunized dams were statistically significant (P = 0.0001 and P = 0.0136, respectively). When the pups from MNA-ZIKV-rEfl-and PBS-immunized dams were compared, no significant difference in survival rate was observed (P = 0.1493), indicating that the Ad5.ZIKV-Efl vaccine candidates were efficient in passively protecting neonatal mice against lethal ZIKV challenge.