Venezuelan equine encephalitis-specific immunoglobulin responses: Live attenuated TC-83 versus inactivated C-84 vaccine

Venezuelan equine encephalitis (VEEI‐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. ELSA 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, GI, 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 inc