ALFQ adjuvanted HIV-1 envelope protein vaccination elicits durable functional antibody and cellular responses in nonhuman primates

Shikha Shrivastava; Joshua M Carmen; Jiae Kim; Kristina K Peachman; Shraddha Basu; Ryan Alving; Danielle Nettere; Gautam Kundu; Lauren Yum; Mohammad Arif Rahman; Shalini Jha; Hung V Trinh; Lorean Rosado; Phuong Nguyen; Elaine Morrison; Isabella Swafford; Kawthar Machmach; Jessica S Bolton; Adam Yates; Elina Misicka; Zoltan Beck; Simona Mutascio; Ousman Jobe; Michelle Zemil McCrea; Lindsay Wieczorek; Elke S Bergmann-Leitner; Victoria Polonis; Dominic Paquin-Proulx; Justin Pollara; Gary R Matyas; Carl R Alving; Rasmi Thomas; Genoveffa Franchini; Guido Ferrari; Barton F Haynes; Julie A Ake; Mangala Rao

doi:10.1038/s41541-025-01322-7

ALFQ adjuvanted HIV-1 envelope protein vaccination elicits durable functional antibody and cellular responses in nonhuman primates

NPJ Vaccines. 2025 Dec 19;11(1):1. doi: 10.1038/s41541-025-01322-7.

Authors

Shikha Shrivastava^{1

2

3

4}, Joshua M Carmen^{1

2

5}, Jiae Kim^{1

2

3}, Kristina K Peachman^{1

2

3

6}, Shraddha Basu^{1

2

3}, Ryan Alving^{1

2

7}, Danielle Nettere⁸, Gautam Kundu^{1

2

3}, Lauren Yum^{1

2

3}, Mohammad Arif Rahman⁹, Shalini Jha⁸, Hung V Trinh^{1

2

3}, Lorean Rosado^{1

2

3}, Phuong Nguyen^{1

2

3}, Elaine Morrison^{1

2}, Isabella Swafford^{1

2

3}, Kawthar Machmach^{1

2

3}, Jessica S Bolton¹⁰, Adam Yates³, Elina Misicka³, Zoltan Beck^{1

2

3}, Simona Mutascio^{1

2

3}, Ousman Jobe^{1

2

3}, Michelle Zemil McCrea^{1

2

3}, Lindsay Wieczorek^{1

2

3}, Elke S Bergmann-Leitner¹¹, Victoria Polonis^{1

2}, Dominic Paquin-Proulx^{1

2

3}, Justin Pollara⁸, Gary R Matyas^{1

2}, Carl R Alving^{1

2}, Rasmi Thomas^{1

2}, Genoveffa Franchini⁹, Guido Ferrari⁸, Barton F Haynes¹², Julie A Ake^{1

2}, Mangala Rao^{13

14}

Affiliations

¹ US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
² Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
³ Henry Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD, USA.
⁴ Viral Vaccines Branch, Pfizer; Pearl River, New York, NY, USA.
⁵ Technical Integration and Defense Division, Pentagon Force Protection Agency, Pentagon, VA, USA.
⁶ Diagnostics and Countermeasures Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁷ Oak Ridge Institute of Science and Education, Oak Ridge, TN, USA.
⁸ Duke University Medical Center, Duke Human Vaccine Institute and Department of Surgery, Durham, NC, USA.
⁹ Animal Models and Retroviral Vaccines Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
¹⁰ Agile Vaccines and Therapeutics, Navy Medical Research Center, Silver Spring, MD, USA.
¹¹ Biologics Research and Development Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
¹² Duke University School of Medicine, Duke Human Vaccine Institute, Departments of Medicine and Integrative Immunobiology, Durham, NC, USA.
¹³ US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA. mrao@hivresearch.org.
¹⁴ Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA. mrao@hivresearch.org.

Abstract

Adjuvants play an important role in modulating antigen-specific immune responses. We conducted a comparative adjuvant immunogenicity study in Rhesus macaques using HIV-1 subtype B gp120 envelope protein, B.63521, formulated with aluminum hydroxide gel (AH), or a family of liposomal adjuvants known as Army Liposome Formulation (ALF). ALF comprises saturated phospholipids, cholesterol, and monophosphoryl lipid A. Inclusion of QS-21 or adsorption of the antigen to AH, followed by the addition of ALF, generates ALFQ and ALFA, while inclusion of both immunostimulants generates ALFQA. Priming with canarypox vector ALVAC, followed by boosting with ALVAC and gp120 formulated with each of the four adjuvants, resulted in ALFQ and ALFQA outperforming AH and ALFA vaccine formulations with a high frequency of antigen-specific plasma cells in the bone marrow, robust antibodies, and Env-specific polyfunctional CD8⁺ T cell responses. Transcriptomic analyses revealed upregulation of antiviral and innate immune pathways, thus highlighting ALFQ as a highly potent adjuvant.

Abstract

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