Comparison of co-immunization of DNA and protein in the same anatomical sites and in contralateral sites to identify mechanisms of protective immune response

• Published in: Journal of the International AIDS Society Vol. 24; no. S1; p. 30
• Main Authors: Felber, B, Lu, Z, Hu, X, Valentin, A, Rosati, M, Weiner, J.A, Shen, X, Tomaras, G.D, Labranche, C, Montefiori, D.C, Williams, W.B, Saunders, K.O, Reed, S.G, Venzon, D.J, Shaw, G.M
• Format: Journal Article
• Language: English
• Published: International AIDS Society 01.01.2021
• Subjects: AIDS vaccines; Genetic aspects; Health aspects; HIV infection; Immune response; Prevention; Testing; Viral proteins; United States
• ISSN: 1758-2652; 1758-2652
• DOI: 10.1002/jia2.25659

Background: We hypothesized that simultaneous recognition of immunogens delivered as DNA and protein by the draining lymph node may impact the quality of the vaccine-induced immune responses. To address this hypothesis, we compared the protective efficacy of an HIV vaccine comprised of DNA (env and gag) and Env proteins by co-administration of both components in the same muscle or by delivering the two vaccine components (DNA and Protein) separated in contralateral sites. Methods: Female rhesus macaques (20 animals/group) were immunized with a 6-valent vaccine including DNA plasmids expressing membrane-anchored gp145 Env sequentially isolated from a HIV-1 infected individual (CH505). The DNA was delivered by IM injection followed by in vivo electroporation. The vaccine also included a gp120 Env protein component adjuvanted in GLA-SE matching the sequences encoded by the plasmid DNA. The DNA and protein vaccine components were administered in the same anatomical sites ('Co-administration group') or in contralateral sites ('Separate Administration group'). After vaccination, the macaques were challenged by weekly intravaginal exposures with low dose T/F tier-2 SHIV CH505 stock. Detailed flow and proteomics/transcriptomics analysis was performed. Results: Only the co-administration vaccine group was protected against SHIV CH505 acquisition, with a 67% risk reduction per exposure after 15 weekly intravaginal challenges. Macaques in the co-administration group developed higher Env-specific humoral and cellular immune responses. Non-neutralizing anti-Env antibodies, ADCC and anti-Env antibodies with strong binding affinity to Fc-gamma Receptor IIIa were associated with decreased transmission risk. Analysis of vaccine-induced and innate immune responses and their association with mechanisms contributing to protection will be discussed. Follow-up boosting of the protected animals showed that the immune response can be further enhanced and the antibody specificity can be broadened. Conclusions: Co-immunization of DNA+Protein in the same muscle induces rapid and effective immunity able to protect from tier-2 SHIV challenge. These data suggest that simultaneous recognition, processing and presentation of DNA+ Env protein in the same draining lymph node plays a critical role in the development of protective immunity. This vaccine regimen, using simultaneously DNA and protein administration, could also be beneficial in protecting against other pathogens.