569. Increased Antigen-Specific Humoral Response by Adenoviral Vector Prime and Adeno-Associated Viral Vector Boost

Abstract

Top of pageAbstract Dissemination of anthrax spores in a bioweapons event could result in inhalational anthrax, a disease that resulted in 45% mortality in the recent US anthrax attacks. The current licensed vaccine and the experimental vaccine currently being assessed by the US Army elicit protective immune responses against protective antigen (PA), a component of lethal toxin. We have recently demonstrated (Tan et al, Human Gene Therapy 2003; 14:1673-1682) that a recombinant serotype 5 adenovirus vector expressing a synthetic gene for PA (Ad5sechPA) offers more robust protection against anthrax lethal toxin challenge than that achieved with purified recombinant PA protein. In this study we have tested the hypothesis that the efficacy of Ad5sechPA vaccination can be enhanced in prime-boost vaccination regimens. BALB/c mice were given intramuscular injections of the Ad5sechPA vaccine at a dose 107, 108, 109 particle units (pu) either once at wk 0, or twice at wk 0 and 4. Anti-PA IgG titer (by ELISA) and neutralizing antibody titer (NAb; reciprocal titer required for 50% inhibition of cytotoxicity by macrophage protection assay) were assessed and lethal toxin challenge was given at wk 6. In all dose groups, boost led to a higher reciprocal anti-PA ELISA titer in pooled sera rising from 200 to 670 in the 107 pu group; from 1,730 to 32,800 in the 108 group and from 2,550 to 40,200 in the 109 group (5 mice/group). Additionally, in all dose groups, boost led to a higher reciprocal neutralizing titer rising from undetectable to 35 in the 107 pu group; from 120 to 810 in the 108 group and from 120 to 1,400 in the 109 group (pooled sera from 5 mice/group). In response to lethal toxin challenge, boost immunization significantly increased protection: 100% of mice in the 108 pu prime-boost group survived the challenge compared to only 20% survival in the 108 pu single immunization group. In the 107 group there was no survival with or without boost and in the 109 group there was 100% survival regardless of boost. We conclude that an Ad5-based anthrax vaccine can be effectively used in prime-boost immunization to achieve more robust protective immunity than single immunization, at least when given via intramuscular route. These results have implications for applying Ad5-based vaccines to human populations.