Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector function magnitude but not durability

Author:

Shubin Zhanna12,Stanfield-Oakley Sherry3,Puangkaew Jiraporn4,Pitisutthithum Punnee5,Nitayaphan Sorachai4,Gurunathan Sanjay6,Sinangil Faruk7,Chariyalertsak Suwat89,Phanuphak Nittaya10,Ake Julie A.1,O’Connell Robert J.14,Vasan Sandhya12,Akapirat Siriwat4,Eller Michael A.12,Ferrari Guido3,Paquin-Proulx Dominic12

Affiliation:

1. U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring

2. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD

3. Department of Surgery, Duke University Medical Center, Durham, NC, USA

4. Armed Forces Research Institute for Medical Sciences

5. Mahidol University, Bangkok, Thailand

6. Sanofi Pasteur, PA

7. Global Solutions for Infectious Diseases, CA, USA

8. Research Institute for Health Sciences

9. Faculty of Public Health, Chiang Mai University, Chiang Mai

10. SEARCH, Institution of HIV Research and Innovation, Bangkok, Thailand.

Abstract

Objectives: The RV144 vaccine trial resulted in a decreased risk of HIV acquisition that was associated with a nonneutralizing antibody response. The objective of this study was to determine the impact of an additional boost to the RV144 vaccine regimen on antibody effector function and durability. Design: RV306 was a randomized, double-blind late boosting of the RV144 prime-boost regimen in HIV-uninfected Thai adults (NCT01931358). This analysis included study participants who received the RV144 vaccine regimen and received no additional boost (group 1) or were boosted with ALVAC-HIV and AIDSVAX (group 2) or only AIDSVAX alone (group 3) 24 weeks after completing the RV144 series. Methods: Plasma samples from RV306 study participants were used to measure antibody-dependent cellular phagocytosis (ADCP), antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent complement deposition (ADCD), antibody-dependent cellular cytotoxicity (ADCC), trogocystosis, and gp120-specifc IgG subclasses. Results: Additional boosting increased the magnitude of all Fc-mediated effector functions 2 weeks following the additional boost compared with 2 weeks after completing the RV144 regimen. However, only trogocytosis remained higher 24–26 weeks after the last vaccination for the study participants receiving an additional boost compared with those that did not receive an additional boost. The additional boost increased IgG1 and IgG4 but decreased IgG3 gp-120 specific antibodies compared with 2 weeks after completing the RV144 regimen. Conclusion: Additional boosting of RV144 improved the magnitude but not the durability of some Fc-mediated effector functions that were associated with vaccine efficacy, with trogocytosis being the most durable.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Infectious Diseases,Immunology,Immunology and Allergy

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