This study is a single-center, randomized, double-blinded, placebo-controlled, Phase 1, dose de-escalation study to evaluate the safety, reactogenicity, and immunogenicity of a purified inactivated, alum-adjuvanted ZIKV vaccine (ZPIV) administered in a homologous prime-boost regimen to healthy male and non-pregnant female adult subjects living in a flavivirus-endemic area. This study will enroll 90 subjects between the ages of 21 and 49 and will be conducted at Ponce Medical School Foundation, Inc.-CAIMED in Ponce, Puerto Rico. The entire duration of each subject's participation is approximately 26 months including recruitment and collection of data on the safety and reactogenicity of the study vaccine and collection of samples for the assessment of immunogenicity. This study is expected to take approximately 49 months to complete. Two dose levels will be evaluated. Each subject will receive either placebo or 5 mcg (Group 1) or 2.5 mcg (Group 2) of ZPIV administered by intramuscular (IM) injection on Days 1 and 29. The study will consist of a screening period of up to 28 days, a vaccination period in which subjects will receive a prime dose of vaccine on Day 1 followed by a homologous boost on Day 29, and a follow-up period of 24 months post boost vaccination. The study will begin with enrollment of 2 sentinel subjects in Group 1 who will receive 5 mcg ZPIV open label. One sentinel subject will be vaccinated, followed for one day for safety and reactogenicity, and if no halting rules are met per determination of the PI and co-PI, then the second sentinel subject will receive 5 mcg ZPIV open-label. Both sentinels will be followed for safety through Day 8 and if no predefined halting rules are met and no safety concerns are identified, then enrollment of the Group 1 non-sentinel subjects will proceed in double-blind fashion. The same procedure will be used for administration of the boost vaccination to the Group 1 sentinels: 1 sentinel (can be either) will receive 5 mcg ZPIV open-label, be followed for one day for safety and reactogenicity, and if no halting rules are met, then the 2nd sentinel will receive the boost vaccine. Both sentinels will be followed until Day 8 after 2nd vaccination for safety and reactogenicity and if no halting rules are met, then boost vaccination of the Group 1 non-sentinel subjects can proceed. Enrollment of the 2.5 mcg ZPIV group (Group 2) can begin after or at the same time non-sentinel subjects in Group 1 receive the 1st dose of vaccine. As of December 18, 2017, the majority of non-sentinel subjects in Group 1 have already received the 1st dose and have been followed until Day 8 for safety and reactogenicity, and no halting rules have been met or safety concerns identified. As this is a dose de-escalation study, concurrent enrollment of some remaining non-sentinel subjects in Groups 1 is permitted after enrollment of Group 2 subjects has begun; also, no sentinel subjects will be used in Group 2. All subjects in Group 2 will receive study product or placebo in double-blind fashion. The original study design planned to enroll 40 ZPIV recipients and 5 placebo recipients in each Group. However, due a natural disaster (hurricane Maria), 11 subjects enrolled in Group 1 had loss of samples at key timepoints. To rebalance the number of evaluable subjects between Groups, Group 1 enrollment will be increased by 5 subjects and Group 2 enrollment will be decreased by 5 subjects, for a total enrollment of 50 subjects in Group 1 and 40 in Group 2. Treatment assignments for both groups will be assigned according to the originally planned 8:1 ratio of ZPIV: placebo. Without compromising the blind of the study, we can anticipate approximately 35 evaluable ZPIV recipients and approximately 5 evaluable placebo recipients in each group. All subjects will receive a homologous boost of ZPIV or placebo 28 days post-prime if no halting rules precluding second vaccination are met (Section 9). All subjects will be monitored for occurrence of unsolicited AEs until 28 days after the second vaccination SAEs, AESIs, and history of new medical conditions with onset after the first vaccination will be collected for the duration of the study. Blood for evaluation of antibodies to ZIKV by ELISA and neutralizing antibody assays will be collected at Visit 00, prior to each vaccination, and at multiple timepoints afterward. Primary objectives are: 1) Assess the safety and reactogenicity of a homologous prime boost regimen of ZPIV given at two different dose levels in a dose de-escalation format in healthy adult subjects who live in Puerto Rico, a flavivirus endemic area. 2) Compare the safety and reactogenicity profile of ZPIV after each vaccination, between dosage groups, and by pre-vaccination flavivirus immune status. Secondary Objectives are: 1) Assess the humoral immune response to a homologous prime-boost regimen of ZPIV after each dose of vaccine as determined by kinetics of the immune responses, seroconversion rates, and Geometric Mean Titers (GMT) overall, and compare results between dosage groups and by pre-vaccination flavivirus immune status. 2) Assess the durability of the humoral immune response to ZPIV at 6, 12, 18, and 24 months after the second vaccine administration overall, and compare results between dosage groups and by pre-vaccination flavivirus immune status.