An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults

Abstract

Background West Nile virus (WNV) is the most common mosquito-borne infection in the United States. HydroVax-001 WNV is a hydrogen peroxide inactivated, whole virion (WNV-Kunjin strain) vaccine adjuvanted with aluminum hydroxide. Methods We performed a phase 1, randomized, placebo-controlled, double-blind (within dosing group), dose escalation clinical trial of the HydroVax-001 WNV vaccine administered via intramuscular injection. This trial evaluated 1 mcg and 4 mcg dosages of HydroVax-001 WNV vaccine given intramuscularly on day 1 and day 29 in healthy adults. The two dosing groups of HydroVax-001 were enrolled sequentially and each group consisted of 20 individuals who received HydroVax-001 and 5 who received placebo. Safety was assessed at all study days (days 1, 2, 4 and 15 post dose 1, and days 1, 2, 4, 15, 29, 57, 180 and 365 post dose 2), and reactogenicity was assessed for 14 days after administration of each dose. Immunogenicity was measured by WNV-specific plaque reduction neutralization tests (PRNT 50 ) in the presence or absence of added complement or by WNV-specific enzyme-linked immunosorbent assays (ELISA). Results HydroVax-001 was safe and well-tolerated as there were no serious adverse events or concerning safety signals. At the 1 mcg dose, HydroVax-001 was not immunogenic by PRNT 50 but elicited up to 41% seroconversion by WNV-specific ELISA in the per-protocol population (PP) after the second dose. At the 4 mcg dose, HydroVax-001 elicited neutralizing antibody responses in 31% of the PP following the second dose. In the presence of added complement, PRNT 50 seroconversion rates increased to 50%, and 75% seroconversion was observed by WNV-specific ELISA. Conclusions The HydroVax-001 WNV vaccine was found to be modestly immunogenic and welltolerated at all dose levels.

Twenty Years of Progress Toward West Nile Virus Vaccine Development

“…Twenty individuals aged 18–49 received 1 µg of HydroVax-001 by the i.m. route and twenty received 4 µg [82]. The vaccine was given in two doses, four weeks apart.…”

Evervac: phase I/II study of immunogenicity and safety of a new adjuvant-free TBE vaccine cultivated in Vero cell culture

“…These considerations motivated researchers to pursue the development of a new generation of classic inactivated flavivirus vaccines using Vero cell line as a substrate. 29,30 The new inactivated vaccine Evervac based on the strain Sofjin of the Far Eastern TBEV subtype was developed at the Chumakov Federal Scientific Center. Vero cell line obtained from the WHO reference cell bank was used as a substrate for the virus reproduction.…”

“…These considerations motivated researchers to pursue the development of a new generation of classic inactivated flavivirus vaccines using Vero cell line as a substrate. 29 , 30 …”

West Nile virus vaccines – current situation and future directions

“…The authors indicate that this result might be improved by adding a third dose or by using an alternative inactivation protocol which combines hydrogen peroxide and formaldehyde. 20 Secondly, three doses of formaldehyde inactivated WNV particles induced high titers of neutralizing antibodies. 21 None of these WNV vaccine trials reported any adverse events or safety concerns which could impede further clinical testing.…”