IDLV-HIV-1 Env vaccination in non-human primates induces affinity maturation of antigen-specific memory B cells

Maria Di Blasi ,Donatella Negri,Robert Parks,Andrea Cara,Zuleika Michelini,Sampa Santra,Xiaoying Shen,Erich J Baker,Nathan Vandergrift ,M Anthony Moody ,Celia C Labranche ,E Brunner ,Kevin Wiehe ,David C Montefiori,Mattia Bonsignori,S Munir Alam,Guido Ferrari,Morgan A Gladden,Barton F Haynes,Georgia D Tomaras,Mary E Klotman

doi:10.1038/s42003-018-0131-6

Abstract

HIV continues to be a major global health issue. In spite of successful prevention interventions and treatment methods, the development of an HIV vaccine remains a major priority for the field and would be the optimal strategy to prevent new infections. We showed previously that a single immunization with a SIV-based integrase-defective lentiviral vector (IDLV) expressing the 1086.C HIV-1-envelope induced durable, high-magnitude immune responses in non-human primates (NHPs). In this study, we have further characterized the humoral responses by assessing antibody affinity maturation and antigen-specific memory B-cell persistence in two vaccinated macaques. These animals were also boosted with IDLV expressing the heterologous 1176.C HIV-1-Env to determine if neutralization breadth could be increased, followed by evaluation of the injection sites to assess IDLV persistence. IDLV-Env immunization was associated with persistence of the vector DNA for up to 6 months post immunization and affinity maturation of antigen-specific memory B cells.

Highlights

HIV continues to be a major global health issue
We have recently shown in non-human primates (NHPs) that a single immunization with integrase-defective lentiviral vector (IDLV) induced functional and durable antigen-specific immune responses that were strongly boosted by a second dose of the same vector[5]
Adenoviral vectors have been shown to be highly immunogenic and to induce robust cytotoxic T lymphocyte responses but their effectiveness has been limited by pre-existing host immunity[28], and vaccine regimens based on Ad5 showed no protective efficacy in the STEP, Phambili, or HVTN 505 studies[29]

Summary

Introduction

HIV continues to be a major global health issue. In spite of successful prevention interventions and treatment methods, the development of an HIV vaccine remains a major priority for the field and would be the optimal strategy to prevent new infections. We have further characterized the humoral responses by assessing antibody affinity maturation and antigen-specific memory B-cell persistence in two vaccinated macaques These animals were boosted with IDLV expressing the heterologous 1176.C HIV-1-Env to determine if neutralization breadth could be increased, followed by evaluation of the injection sites to assess IDLV persistence. We have recently shown in non-human primates (NHPs) that a single immunization with IDLV induced functional and durable (up to 1 year) antigen-specific immune responses that were strongly boosted by a second dose of the same vector[5]. In the present study we have assessed the effect of a single IDLV containing a heterologous envelope (Env) as a boosting injection in the same cohort of vaccinated NHPs and have analyzed both antibody affinity maturation and antigen-specific memory B-cell persistence. We found that IDLV immunization induced continued antibody affinity maturation 3 months post prime, with additional affinity maturation after the second IDLV immunization

Methods

Results

Conclusion