Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization

• Published in: PloS one Vol. 12; no. 10; p. e0186602
• Main Authors: C Guardo, Alberto, Gómez, Carmen Elena, Díaz-Brito, Vicens, Pich, Judit, Arnaiz, Joan Albert, Perdiguero, Beatriz, García-Arriaza, Juan, González, Nuria, Sorzano, Carlos O S, Jiménez, Laura, Jiménez, José Luis, Muñoz-Fernández, María Ángeles, Gatell, José M, Alcamí, José, Esteban, Mariano, López Bernaldo de Quirós, Juan Carlos, García, Felipe, Plana, Montserrat
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.10.2017; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS vaccines; AIDS Vaccines - adverse effects; AIDS Vaccines - immunology; Antibodies; Antibodies, Neutralizing - immunology; Antigens; Binding; Bioengineering; Biology and Life Sciences; Biomedical materials; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Clinical trials; Deoxyribonucleic acid; DNA; Durability; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gag protein; Genomes; Glycoprotein gp120; Healthy Volunteers; HIV; HIV Antibodies - blood; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immune response; Immune response (humoral); Immunization; Immunization, Secondary; Immunogenicity; Immunology; Infectious diseases; Interferon; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Neutralizing; Physiological aspects; Placebos; Research and Analysis Methods; Safety; Safety and security measures; Vaccines; Viruses; γ-Interferon; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0186602

We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. End-points were safety, cellular and humoral immune responses to HIV-1 and vector antigens assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed before and 2, 4 and 12 weeks after receiving the boost. Volunteers reported 64 adverse events (AEs), although none was a vaccine-related serious AE. After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in IFN-γ T-cell responses, mainly directed against Env, was detected by ELISPOT in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+ T cell-responses were similarly distributed against Env, Gag and GPN. In terms of antibody responses, 23.1% of the vaccinees had detectable Env-specific binding antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5. The late MVA-B boost significantly improved both the response rate (92.3%) and the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460). HIV-1 neutralizing antibodies were also enhanced and detected in 77% of volunteers. Moreover, MVA vector-specific T cell and antibody responses were boosted in 80% and 100% of volunteers respectively. One boost of MVA-B four years after receiving 3 doses of the same vaccine was safe, induced moderate increases in HIV-specific T cell responses in 38% of volunteers but significantly boosted the binding and neutralizing antibody responses to HIV-1 and to the MVA vector. ClinicalTrials.gov NCT01923610.