VENEZUELAN EQUINE ENCEPHALITIS-SPECIFIC IMMUNOGLOBULIN RESPONSES - LIVE ATTENUATED TC-83 VERSUS INACTIVATED C-84 VACCINE

Venezuelan equine encephalitis (VEE)-specific immunoglobulin responses to the two vaccines, TC-83 (a live attenuated vaccine) and C-84 (a formalin inactivated vaccine derived from the TC-83 strain of virus) were evaluated using an antigen and isotype-specific enzyme-linked immunoadsorbent assay (ELISA). The VEE-specific ELISA for IgG, IgG subclasses, IgA and IgM were developed and standardized using sera from vaccine-exposed and unexposed human subjects. Paired human sera (before and 28 days after immunization) were tested from laboratory workers vaccinated with either TC-83 (Group A: 20 paired sera from subjects receiving a single TC-83 vaccine and with no prior history of vaccination) or C-84 in varying schedules (Group B: 19 paired sera from subjects who had a distant vaccination history to TC-83 but no evidence of neutralizing antibody; Group C: 19 paired sera from subjects receiving their first C-84 vaccination and no prior documented history of vaccination; Group D: 15 paired sera from subjects receiving a C-84 booster vaccination with prior history of C-84 but no TC-83 exposure). Sera were all tested for viral neutralization in vitro using a Vero cell monolayer for culturing virus and establishing 80% plaque reduction for each serum tested. All pre-sera tested demonstrated no plaque reduction neutralization at a level of 80% for a dilution of 1:10. ELISA antibody titers for all pre-sera with no prior VEE exposure through vaccination or possible environmental factors were negative at a titer of 1:160 for IgM, 1:80 for IgG, IgA, and G subclasses. All vaccine types and strategies generated a significant IgG response postvaccination (P < 0.0001) and this response correlated with the 80% plaque reduction neutralization titer (PRN-80) for VEE-specific IgG, G1, G3 and IgA at a P value of < 0.001 for both Group A and B. No such correlation was observed for G2 and no G4 responses to immunization were noted in any of the groups tested. There was a significant difference between geometric mean (GM) titers postvaccination for Group A or Group B versus Group C (P < 0.001) and for Group C versus Group D (P < 0.001) for IgG. Neither group C or D (1 or 2 doses of C-84 alone) demonstrated an IgA response in contrast to the TC-83 exposed groups (Groups A and B). C-84 was an effective booster vaccine in subjects previously exposed to the live attenuated vaccine and generated a significant neutralization antibody response mirrored in the IgG, G1, G3 and IgA titer increases by ELISA.