We have identified several patient sera showing potent and broad HIV-1 neutralization. Using antibody adsorption and elution from selected gp120 variants, the neutralizing specificities of the two most broadly reactive sera were mapped to the primary receptor CD4-binding region of HIV-1 gp120. Novel antibodies to the CD4-binding site are elicited in some HIV-1-infected individuals, and new approaches to present this conserved region of gp120 to the immune system may result in improved vaccine immunogens.

The filovirus Ebola causes hemorrhagic fever with 70 -80% human mortality. High case-fatality rates, as well as known aerosol infectivity, make Ebola virus a potential global health threat and possible biological warfare agent. Development of an effective vaccine for use in natural outbreaks, response to biological attack, and protection of laboratory workers is a higher national priority than ever before. Coexpression of the Ebola virus glycoprotein (GP) and matrix protein (

The magnitude and durability of immune responses induced by replication-defective adenovirus serotype 5 (ADV5) vector-based vaccines were evaluated in the simian-human immunodeficiency virus/rhesus monkey model. A single inoculation of recombinant ADV5 vector constructs induced cellular and humoral immunity, but the rapid generation of neutralizing anti-Ad5 antibodies limited the immunity induced by repeated vector administration. The magnitude and durability of the immune responses elicited by these vaccines were greater when they were delivered as boosting immunogens in plasmid DNA-primed monkeys than when they were used as single-modality immunogens. Therefore, administration of ADV5-based vectors in DNA-primed subjects may be a preferred use of this vaccine modality for generating long-term immune protection.Accumulating data suggest that an effective human immunodeficiency virus (HIV) vaccine should elicit potent and durable virus-specific cellular and humoral immune responses. Vaccine-elicited immune responses can contribute to ameliorating simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus-induced disease in macaques (1,2,8,9,13,15). However, the durability of the immune responses generated by vaccination may not be adequate to provide clinical protection over a prolonged period of time. In fact, we have recently shown that the immune responses in plasmid DNA-primed rhesus monkeys that were boosted with recombinant poxviruses decayed so rapidly following the boosting immunization that no incremental clinical protection was afforded by the delivery of the live recombinant vector (14). We sought to evaluate the durability of immune responses in rhesus monkeys generated with a plasmid DNA prime/recombinant adenovirus boost vaccine.Serotype 5 human adenovirus made replication incompetent by mutation of the viral E1 and E3 genes (ADV5) has proven a safe and highly immunogenic vector in studies with laboratory animals and early-phase human clinical trials (4, 5, 17). These results have provided a rationale for advancing recombinant ADV5 into efficacy testing in human volunteers (11). However, only limited work has been done to determine the durability of the immunity that can be generated through immunization with these vaccine constructs. The present studies were performed in Indian-origin rhesus monkeys to evaluate the magnitude and persistence of the immune responses generated following recombinant ADV5 immunization. ADV5 vaccine constructs were first evaluated for immunogenicity with or without prior immunization using plasmid DNA. DNA plasmids expressing codon-optimized HIV type 1 (HIV-1) and SIV immunogens were made synthetically, using a method that has been previously described (10). The full-length synthetic SIVmac239 gag-pol-nef gene encoding a fusion protein was cloned in the mammalian expression vector pVR1012 under the control of the cytomegalovirus immediateearly enhancer, promoter, and first intron. The pVR1012-HIV-1 89.6P Env plasmid expresses a modified form of the env ...