IMMUNIZATION WITH A RECOMBINANT ENVELOPE PROTEIN (RGP90) OF EIAV PRODUCES A SPECTRUM OF VACCINE EFFICACY RANGING FROM LACK OF CLINICAL-DISEASE TO SEVERE ENHANCEMENT

We have previously reported that immunization of ponies with a baculov irus-expressed recombinant surface unit envelope protein (rgp90) for e quine infectious anemia virus (EIAV) resulted in enhancement of diseas e symptoms and virus replication in 4 of 4 vaccine recipients subjecte d to a heterologous virus challenge (rgp90 I vaccine trial) (Wang et a l., 1994). To extend these studies of EIAV vaccine enhancement, two ad ditional and independent rgp90 vaccine trials (rgp90 II and rgp90 III) were performed. Combined, a total of 13 ponies were immunized with th e rgp90 immunogen using our standard vaccination procedures and challe nged with a heterologous strain of EIAV. In contrast to the uniform en hancement observed in the rgp90 I vaccine trial, the severity of clini cal symptoms varied markedly among the rgp90 recipients: 5 ponies expe rienced enhanced disease symptoms, 5 ponies experienced moderate disea se symptoms, and 3 ponies remained asymptomatic. Of particular interes t, in the 5 ponies with enhanced clinical symptoms was a severe thromb ocytopenia (less than or equal to 105.000 platelets/mu l) evident coin cident with the first febrile episode following virus challenge. Throm bocytopenia was either absent (7/10 ponies) or substantially delayed ( 3/10 ponies) in naive control ponies inoculated with the standard EIAV (PV) challenge. Measurements of virus replication in the challenged va ccine recipients indicated a correlation between the level of viral RN A in plasma and the severity of the disease. Interestingly, an associa tion was not observed between serum antibody reactivity to the vaccine or native viral antigens and the frequency of enhancement. Thus, thes e observations demonstrate a previously unrecognized complexity of rgp 90 vaccine efficacy that has important implications for AIDS vaccine d evelopment. (C) 1998 Academic Press.