Inactivated Venezuelan equine encephalomyelitis virus vaccine complexed with specific antibody: enhanced primary immune response and altered pattern of antibody class elicited.

Complexes of formalinized Venezuelan equine encephalomyelitis (VEE) virus vaccine and specific IgG formed at antigen-antibody equivalence enhanced the immune responses of rhesus monkeys (Macaca mulatta). The predomonant class of antibody elicited by complexes was IgG. In contrast, lower titers of antibody and a more biphasic (IgG-IgM) response were observed after exposure of monkeys to the vaccine alone. In comparison to the response of monkeys primed with antigen, a more rapid secondary response was obtained in monkeys primed with the complexes of antigen and antibody formed at equivalence. A sustained level of protection of 88% was afforded mice 24 hr after immunization with antigen-antibody complexes; development of protection after administration of antigen required eight days to reach this level. Passive protection (80%-100%) was conferred by IgG controls for seven to eight days after immunization. This level of protection was not significantly affected by X-irradiation 24 hr prior to administration of IgG; however, protection in mice similarly irradiated prior to immunization with antigen-antibody complexes was significantly decreased. Early protection afforded by the complexes was not nonspecific (interferon) but was mediated by specific immunologic mechanisms and may be caused by an early formation of IgG.

Modified polyriboinosinic-polyribocytidylic acid, an immunological adjuvant.

Stabilization of polyriboinosinic-polyribocytidylic acid against enzymatic hydrolysis by addition of poly-1-lysine and carboxymethylcellulose (PICLC) resulted in a compound with marked adjuvanticity. The primary antibody response of rhesus monkeys to formalin-inactivated Venezuelan equine encephalomyelitis virus vaccine was significantly potentiated if the vaccine was combined with PICLC prior to vaccination. The antibody response was maintained at a significantly higher level than controls for 2.5 months postvaccination and paralleled immunological responses reported for live, attenuated (TC-83) vaccine.

Adjuvant effects of diethylaminoethyl-dextran.

Diethylaminoethyl-dextran exhibited a significant effect on the primary immune response of rhesus monkeys to formalin-inactivated Venezuelan equine encephalomyelitis virus vaccine (IVEE). Antibody formed to IVEE and adjuvant followed a classic immunoglobulin M-immunoglobulin G pattern; however, as compared with vaccine alone, use of this adjuvant with IVEE reduced the time required for onset of immunoglobulin G synthesis.

Effects of antigen-antibody complexes on the primary immune response in Rhesus monkeys.

A model for the enhancement of the primary humoral immune response of rhesus monkeys to marginal or weakly antigenic vaccines is presented. Our procedure used the complexing of formalin-inactivated Venezuelan equine encephalomyelitis (VEE) virus vaccine with specific, homologous, immune gamma globulin (IgG) at equivalence. Equivalence was determined by combining the concentrated, isotopically labeled ((3)H) virus with various concentrations of specific Sephadex-fractionated IgG. Enhancement of VEE virus antibody response in monkeys was obtained from preparations containing a marginal concentration of antigen that was complexed at equivalence with homologous IgG as compared with antigen alone. Protection in Swiss mice closely paralleled the antibody response pattern observed in monkeys, since complexes at equivalence provided 30 to 50% greater protection against challenge than antigen alone.