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

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 MisickaZoltan 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^*

^*Corresponding author for this work

Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	1
Journal	npj Vaccines
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41541-025-01322-7
State	Published - Dec 2026

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Shrivastava, S., Carmen, J. M., Kim, J., Peachman, K. K., Basu, S., Alving, R., Nettere, D., Kundu, G., Yum, L., Rahman, M. A., Jha, S., Trinh, H. V., Rosado, L., Nguyen, P., Morrison, E., Swafford, I., Machmach, K., Bolton, J. S., Yates, A., ... Rao, M. (2026). ALFQ adjuvanted HIV-1 envelope protein vaccination elicits durable functional antibody and cellular responses in nonhuman primates. npj Vaccines, 11(1), Article 1. https://doi.org/10.1038/s41541-025-01322-7

@article{cd53fe74cba049099d42e6e7abd4d335,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025.",

year = "2026",

month = dec,

doi = "10.1038/s41541-025-01322-7",

language = "English",

volume = "11",

journal = "npj Vaccines",

issn = "2059-0105",

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Shrivastava, S, Carmen, JM, Kim, J, Peachman, KK, Basu, S, Alving, R, Nettere, D, Kundu, G, Yum, L, Rahman, MA, Jha, S, Trinh, HV, Rosado, L, Nguyen, P, Morrison, E, Swafford, I, Machmach, K, Bolton, JS, Yates, A, Misicka, E, Beck, Z, Mutascio, S, Jobe, O, Zemil McCrea, M, Wieczorek, L, Bergmann-Leitner, ES, Polonis, V, Paquin-Proulx, D, Pollara, J, Matyas, GR, Alving, CR, Thomas, R, Franchini, G, Ferrari, G, Haynes, BF, Ake, JA & Rao, M 2026, 'ALFQ adjuvanted HIV-1 envelope protein vaccination elicits durable functional antibody and cellular responses in nonhuman primates', npj Vaccines, vol. 11, no. 1, 1. https://doi.org/10.1038/s41541-025-01322-7

TY - JOUR

T1 - ALFQ adjuvanted HIV-1 envelope protein vaccination elicits durable functional antibody and cellular responses in nonhuman primates

AU - Shrivastava, Shikha

AU - Carmen, Joshua M.

AU - Kim, Jiae

AU - Peachman, Kristina K.

AU - Basu, Shraddha

AU - Alving, Ryan

AU - Nettere, Danielle

AU - Kundu, Gautam

AU - Yum, Lauren

AU - Rahman, Mohammad Arif

AU - Jha, Shalini

AU - Trinh, Hung V.

AU - Rosado, Lorean

AU - Nguyen, Phuong

AU - Morrison, Elaine

AU - Swafford, Isabella

AU - Machmach, Kawthar

AU - Bolton, Jessica S.

AU - Yates, Adam

AU - Misicka, Elina

AU - Beck, Zoltan

AU - Mutascio, Simona

AU - Jobe, Ousman

AU - Zemil McCrea, Michelle

AU - Wieczorek, Lindsay

AU - Bergmann-Leitner, Elke S.

AU - Polonis, Victoria

AU - Paquin-Proulx, Dominic

AU - Pollara, Justin

AU - Matyas, Gary R.

AU - Alving, Carl R.

AU - Thomas, Rasmi

AU - Franchini, Genoveffa

AU - Ferrari, Guido

AU - Haynes, Barton F.

AU - Ake, Julie A.

AU - Rao, Mangala

PY - 2026/12

Y1 - 2026/12

N2 - 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.

AB - 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.

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U2 - 10.1038/s41541-025-01322-7

DO - 10.1038/s41541-025-01322-7

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