Immune interference in the setting of same-day administration of two similar inactivated alphavirus vaccines: eastern equine and western equine encephalitis.

We compared the effect on primary vaccination plaque-reduction neutralization 80% titers (PRNT80) responses of same-day administration (at different injection sites) of two similar investigational inactivated alphavirus vaccines, eastern equine encephalitis (EEE) vaccine (TSI-GSD 104) and western equine encephalitis (WEE) vaccine (TSI-GSD 210) to separate administration. Overall, primary response rate for EEE vaccine was 524/796 (66%) and overall primary response rate for WEE vaccine was 291/695 (42%). EEE vaccine same-day administration yielded a 59% response rate and a responder geometric mean titer (GMT)=89 while separate administration yielded a response rate of 69% and a responder GMT=119. WEE vaccine same-day administration yielded a 30% response rate and a responder GMT=53 while separate administration yielded a response rate of 54% and a responder GMT=79. EEE response rates for same-day administration (group A) vs. non-same-day administration (group B) were significantly affected by gender. A logistic regression model predicting response to EEE comparing group B to group A for females yielded an OR=4.10 (95% CL 1.97-8.55; p=.0002) and for males yielded an OR=1.25 (95% CL 0.76-2.07; p=.3768). WEE response rates for same-day administration vs. non-same-day administration were independent of gender. A logistic regression model predicting response to WEE comparing group B to group A yielded an OR=2.14 (95% CL 1.22-3.73; p=.0077). We report immune interference occurring with same-day administration of two completely separate formalin inactivated viral vaccines in humans. These findings combined with the findings of others regarding immune interference would argue for a renewed emphasis on studying the immunological mechanisms of induction of inactivated viral vaccine protection.

Immunogenicity of an inactivated Japanese encephalitis vaccine (JE-VAX) in humans over 20 years at USAMRIID: using PRNT50 as an endpoint for immunogenicity.

Two hundred and ninety-three subjects received a three-dose primary JE-VAX series and had post-primary shot 3 titers within 56 days at USAMRIID from 1985 to 2005. Overall, the PRNT50 primary response rate (titer of 1:10 or greater) was 269/293 (92%). Eighteen out of 19 subjects (95%) responded with adequate PRNT50 titer within 56 days after first JE-VAX boost. Primary PRNT50 responses to JE-VAX varied significantly in response rates and in geometric means (GMT) by vaccine lot. We recommend that future vaccine studies using PRNT as an immunologic endpoint include a coefficient of variation result alongside the GMT to assist in evaluating GMT results. For subjects who responded within 56 days of primary shot 3, 50% experienced a PRNT50 decline in titer to <1:10 at 805 days and a PRNT80 decline in titer to <1:10 at 355 days. Consequently, for individuals traveling to JE endemic areas, we recommend JE-VAX boost every 2 years and for individuals working with high titers of JE virus in the lab setting, we would recommend JE-VAX boost annually.

An outbreak of West Nile virus in a New York City captive wildlife population.

An outbreak of West Nile virus (WNV) in and around New York City during the late summer of 1999 was the cause of extensive mortality among free-ranging birds. Within the Bronx Zoo/Wildlife Conservation Park, viral activity was also observed and produced some morbidity and mortality among specimens in the zoo's bird collection and probably caused morbidity in at least one specimen from the zoo's mammal collection. To determine the extent of the outbreak and attempt to ascertain the temporal appearance of virus within the park, a serologic survey of birds and mammals was performed. The survey showed that 34% of tested birds (125 of 368; 124 species) were positive for antibody to WNV. The virus caused a disease to infection ratio of 22% (27 of 125) among birds with a 70% (19 of 27) case fatality rate. In contrast, only 8% of the mammals (9 of 117; 35 species) possessed antibody to WNV and there was no virus-associated mortality. Testing of banked and fresh sera obtained from both birds and mammals revealed that there was no evidence of WNV circulation before the 1999 outbreak and that birds introduced into the park were not the source of the New York outbreak. West Nile virus RNA was detected in tissues from one bird that died in February 2000, long after the end of the mosquito transmission season. The potential importance of zoologic parks as possible sentinels for emerging diseases is discussed.