All reported local and systemic solicited reactogenicity was mild to moderate in severity
All reported local and systemic solicited reactogenicity was mild to moderate in severity. April 2 and June 13, 2019, 30 trial participants were enrolled (mean age 32 years; 16 [53%] female, 14 [47%] male). Six groups of five participants each received 6, 30, or 60 mcg vaccine doses with or without adjuvant, and all 30 participants completed study follow-up. Vaccinations were safe and well-tolerated. The most frequently reported symptoms were mild injection-site pain and tenderness (22/30 [73%]) and malaise (15/30 [50%]). Dose-dependent differences in the frequency of pain and tenderness were found between the 6, 30, and 60 mcg groups (p= 0022); no significant differences were observed between dosing groups for any other reactogenicity symptom. Two adverse events in one trial AMG 487 participant (60 mcg dose with alum) were assessed as possibly related to the study product; both resolved without clinical sequelae. Four weeks following the second vaccine administration neutralizing antibodies were induced in all study groups with the highest response seen against all three vaccine antigens in the 30 mcg + alum group (PRNT80geometric mean titer: EEEV: 608 [95% CI 299-1240]; VEEV: 1115 [95% CI 498-2498]; WEEV: 1879 [95% CI 900-3922]. Finally, four weeks following second vaccine administration the majority of trial participants developed an immune response to all three vaccine components (EEEV: 24/29 [83%]; VEEV: 26/29, [90%]; WEEV: 27/29, [93%]; EEEV, VEEV, and WEEV: 22/29, [76%]). == Interpretation == Consistent with phase AMG 487 1 trials, the primary limitation of this study is the small sample size. The favorable safety profile and neutralizing antibody responses, along with pressing public health need, support further evaluation of this product in advanced phase clinical trials. == Funding == The Vaccine Research Center of the National Institute of Allergy and Infectious Diseases, National Institutes of Health funded the clinical trial. The United States Department of Defense contributed funding for manufacturing of the study product. == Introduction == Western (WEEV), eastern (EEEV), and Venezuelan (VEEV) equine encephalitis viruses are single-stranded RNA alphaviruses that are highly pathogenic to humans and other vertebrates.1Viral transmission to humans is mediated by more than 20 species of mosquito vectors including Aedes, Coquillettidia, and Culex that are capable of transmitting virus between infected bird or rodent hosts and humans.13These viruses have caused Sema3d small, but recurrent epizootics in North, South, and Central America over the last several decades. The most recent outbreak documented in Central America occurred in Panama in 2010 AMG 487 2010 with 13 confirmed cases of EEEV, 11 cases of VEEV, and one case of coinfection.4However, due to overlap in clinical symptoms with other arboviruses such as Dengue, as well as limitations in surveillance and diagnostics, the true disease burden of these viruses it not clearly understood. 5Sporadic outbreaks of EEEV in humans have also occurred throughout the United States, averaging 11 cases per year between 2009-2018.6,7During 2019, the United States encountered the AMG 487 largest outbreak of EEEV to date with 38 confirmed cases and 15 related deaths predominantly across the northeast.7The clinical manifestation of VEEV, WEEV, or EEEV infection ranges from mild flu-like symptoms to severe neurological illnesses including fatal encephalitis.1,8The estimated case fatality rates associated with infection can be low (<1%) for VEEV, moderate (3-15%) for WEEV, and as high as 70% for EEEV.9The recent outbreaks in the United States and high.