Efficient protein boosting after plasmid DNA or recombinant adenovirus immunization with HIV-1 vaccine constructs

Abstract

DNA plasmids and recombinant adenovirus serotype-5 (rAd5) vectors are being studied in human clinical trials as HIV-1 vaccine candidates. Each elicits robust T-cell responses and modest antibody levels. Since protein immunization alone elicits antibody but not CD8 T-cell responses, we studied protein boosting of DNA and rAd5 HIV-1 vaccine vectors. A single Env protein immunization provided a marked boost in antibody titer in guinea pigs primed with either DNA or rAd5 vaccines, and the resulting antibody binding and neutralization levels were similar to those attained after thee sequential protein immunizations. Since both T-cell immunity and neutralizing antibodies are thought to be required for protection against HIV-1, it may be possible to establish a balanced T-cell and antibody response with appropriate vectored vaccines and improve the neutralizing antibody titer with protein boosting.

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

“…Our preclinical study results also indicated that this combination vaccination approach, but not recombinant protein alone, was effective in eliciting NAbs against primary HIV isolates [19], a finding that has been confirmed subsequently by other independent studies [20][21][22][23][24][25][26]. Furthermore, when polyvalent primary Env antigen formulations were used, the DNA primeprotein boost approach was more effective than the monovalent primary Env antigen in eliciting rabbit NAbs against a wide range of selected primary viral isolates across subtypes A, B, C, D and E [27].…”

Enhancing Blood-Stage Malaria Subunit Vaccine Immunogenicity in Rhesus Macaques by Combining Adenovirus, Poxvirus, and Protein-in-Adjuvant Vaccines

“…High-Ab titers have been reported following heterologous prime-boost regimens using adenovirus-MVA or two adenoviral vectors of heterologous serotype (9,11). We previously reported in mice using vaccines against MSP1 that even higher Ab titers can be achieved by combining vectored vaccines with protein-in-adjuvant vaccines (31), similar to that seen in studies of HIV-1 vaccine candidates (32)(33)(34)(35)(36). The data in this study of two viral-vectored vaccines and protein-in-adjuvant vaccines in rhesus macaques agreed with the previous murine data, demonstrating that moderately high IgG was induced against both alleles of AMA1 by AdCh63-MVA immunization and that even higher titers could be induced by protein-in-adjuvant boosting.…”

“…This represents an important test of the adenovirus-protein and adenovirus-MVA-protein regimens in macaques, prior to evaluation of these promising regimens in clinical trials. Further studies will be needed to compare the titers induced by vector-protein regimens with protein-only regimens in macaques, although other murine and macaque vaccine studies with different constructs have suggested that they may perform comparably (34,37). Interestingly, boosting with protein formulated in CoVaccine HT only led to moderately higher-peak and long-term IgG titers in comparison with formulation in Alhydrogel.…”

Replicating adenovirus vector prime/protein boost strategies for HIV vaccine development

“…Novel boosting immunogens will undoubtedly be needed to elicit broadly neutralizing antibodies. Further, as reported by others [106,107], boosting with protein can lead to increased and broader cellular and humoral immune responses. The studies reviewed to this point all were conducted with two replicating Ad-recombinant priming immunizations followed by two protein boosts.…”