Article
Immunology
Rebecca T. van Dorsten, Kshitij Wagh, Penny L. Moore, Lynn Morris
Summary: The combination of two or three single chain variable fragments (scFv) derived from broadly neutralizing antibodies (bNAbs) shows significantly improved potency and breadth in preventing HIV infection compared to individual scFv. The combinations generally follow an independent action model with no significant synergy or antagonism observed, and the Bliss-Hill model is better at predicting the potency of triple combinations. This suggests that scFv combinations have potential for use in passive immunization.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Simone Conti, Kevin J. Kaczorowski, Ge Song, Katelyn Porter, Raiees Andrabi, Dennis R. Burton, Arup K. Chakraborty, Martin Karplus
Summary: Developing a vaccine that can generate broadly neutralizing antibodies against HIV is crucial in combating the HIV epidemic, but it requires at least three stages. The challenge lies in designing an optimal panel of antigens that can elicit such antibodies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Simone Conti, Kevin J. Kaczorowski, Ge Song, Katelyn Porter, Raiees Andrabi, Dennis R. Burton, Arup K. Chakraborty, Martin Karplus
Summary: Research has shown that a vaccine capable of eliciting broadly neutralizing antibodies against HIV has potential to protect against the virus, involving at least three separate stages. This vaccine may require immunization with a mixture of Envs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Matthijs Meijers, Kanika Vanshylla, Henning Gruell, Florian Klein, Michael Laessig
Summary: Broadly neutralizing antibodies show promise in treating and preventing HIV-1 infections, but the virus often evolves resistance. A fitness model based on in vivo data accurately predicts the dynamics of HIV-1 escape during antibody treatment, highlighting an evolutionary trade-off between antibody resistance and its collateral cost.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Wen Shi Lee, Arnold Reynaldi, Thakshila Amarasena, Miles P. Davenport, Matthew S. Parsons, Stephen J. Kent
Summary: The study found that repeated intravenous doses of PGT121 led to the induction of anti-PGT121 ADA, which in turn resulted in decreased suppression of SHIV viremia.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Daniel J. Sheward, Tandile Hermanus, Ben Murrell, Nigel Garrett, Salim S. Abdool Karim, Lynn Morris, Penny L. Moore, Carolyn Williamson
Summary: The development of broadly neutralizing antibodies (bNAbs) to HIV and other diverse pathogens may require the use of multiple immunogens. This study characterizes the antibody responses in individuals coinfected with multiple HIV variants, revealing interference and the potential role of conserved neutralizing epitopes in guiding broad antibody responses.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Yuanyuan Hu, Sen Zou, Zheng Wang, Ying Liu, Li Ren, Yanling Hao, Shasha Sun, Xintao Hu, Yuhua Ruan, Liying Ma, Yiming Shao, Kunxue Hong
Summary: This study analyzed the evolutionary characteristics and neutralization sensitivity of viruses in HIV-1 subtype B infected patients, revealing that two virus clusters adopted different escape mechanisms under different immune pressures.
Review
Immunology
Sharana Mahomed, Nigel Garrett, Cheryl Baxter, Quarraisha Abdool Karim, Salim S. Abdool Karim
Summary: Passive immunization with bnAbs shows potential in reducing global HIV infections, with newly developed highly potent bnAbs showing promise for HIV prevention. Published data indicate these antibodies are safe and effective, and if proven to be successful, could have a positive impact on HIV vaccine development.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Immunology
Blandine Noailly, Melyssa Yaugel-Novoa, Justine Werquin, Fabienne Jospin, Daniel Drocourt, Thomas Bourlet, Nicolas Rochereau, Stephane Paul
Summary: Broadly neutralizing antibodies (bNAbs) show promising potential for HIV-1 prevention. Different bNAb isotypes have varying abilities in viral neutralization and ADCC-like activity. These findings contribute to the search for new treatments and antibody-based vaccines.
Review
Immunology
Kshitij Wagh, Michael S. Seaman
Summary: Combining broadly neutralizing antibodies (bNAbs) and multispecific therapeutics has the potential to effectively prevent and treat HIV-1 infection. Recent clinical studies have shown that the complementarity of bNAbs can overcome resistance mutations and viral diversity, leading to successful prophylactic and therapeutic strategies. Therefore, next-generation bNAb-based combination or multispecific therapeutics should leverage the complementarity of component bNAbs to maximize potency and breadth for clinical success.
CURRENT OPINION IN HIV AND AIDS
(2023)
Article
Virology
Priyanka Gadam Rao, Gregory S. Lambert, Chitra Upadhyay
Summary: This study aimed to identify exposed/occluded Env epitopes on HIV-1 particles and investigate the mechanisms contributing to their masking. The researchers found that only select epitopes are accessible on virus particles, while others are masked. These masked epitopes can become accessible through pre-binding of specific antibodies or lectin-glycan interactions.
JOURNAL OF VIROLOGY
(2023)
Article
Medicine, General & Internal
Matthew S. Parsons, Anne B. Kristensen, Kevin J. Selva, Wen Shi Lee, Thakshila Amarasena, Robyn Esterbauer, Adam K. Wheatley, Benjamin R. Bavinton, Anthony D. Kelleher, Andrew E. Grulich, Georges Khoury, Jennifer A. Juno, Stephen J. Kent
Summary: The study found that passively infused anti-HIV-1 neutralizing antibody provides protection at semen exposed mucosae, demonstrating a positive effect on rectal SHIVSF162P3 challenge.
Article
Immunology
Elizabeth J. McFarland, Coleen K. Cunningham, Petronella Muresan, Edmund Capparelli, Charlotte Perlowski, Patricia Morgan, Betsy Smith, Rohan Hazra, Lynette Purdue, Paul A. Harding, Gerhard Theron, Hilda Mujuru, Allison Agwu, Murli Purswani, Mobeen H. Rathore, Britta Flach, Alison Taylor, Bob C. Lin, Adrian B. McDermott, John R. Mascola, Barney S. Graham
Summary: The study evaluated the use of VRC01LS in HIV-1 exposed infants, demonstrating good tolerability and pharmacokinetics. The results suggest the potential of using more potent long-acting bNAbs as adjunct treatment with antiretrovirals to prevent infant HIV-1 transmission.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Immunology
Tara Smith, Silvina Masciotra, Wei Luo, Vickie Sullivan, William M. Switzer, Jeffrey A. Johnson, Walid Heneine
Summary: The study identified several diagnostic tests that can differentiate HIV-1 infection events among persons receiving bNAb immunoprophylaxis, providing guidance for diagnostic testing practices.
Review
Immunology
Giacomo Schmidt Frattari, Marina Caskey, Ole Schmeltz Sogaard
Summary: This review focuses on the potential use of broadly neutralizing antibodies (bNAbs) as treatment and cure of HIV. It summarizes the current knowledge, reviews recent clinical studies, and discusses the future applications and strategies involving bNAbs in HIV treatment and cure.
CURRENT OPINION IN HIV AND AIDS
(2023)
Article
Multidisciplinary Sciences
Makda S. Gebre, Susanne Rauch, Nicole Roth, Jingyou Yu, Abishek Chandrashekar, Noe B. Mercado, Xuan He, Jinyan Liu, Katherine McMahan, Amanda Martinot, David R. Martinez, Victoria Giffin, David Hope, Shivani Patel, Daniel Sellers, Owen Sanborn, Julia Barrett, Xiaowen Liu, Andrew C. Cole, Laurent Pessaint, Daniel Valentin, Zack Flinchbaugh, Jake Yalley-Ogunro, Jeanne Muench, Renita Brown, Anthony Cook, Elyse Teow, Hanne Andersen, Mark G. Lewis, Adrianus C. M. Boon, Ralph S. Baric, Stefan O. Mueller, Benjamin Petsch, Dan H. Barouch
Summary: In non-human primates, the second-generation mRNA vaccine CV2CoV was found to induce higher levels of immune responses and provide stronger protection against SARS-CoV-2 variants compared to CVnCoV. The optimization of non-coding regions greatly improved the immunogenicity and protective efficacy of the non-modified mRNA vaccine in non-human primates.
Article
Multidisciplinary Sciences
Jinyan Liu, Abishek Chandrashekar, Daniel Sellers, Julia Barrett, Catherine Jacob-Dolan, Michelle Lifton, Katherine McMahan, Michaela Sciacca, Haley VanWyk, Cindy Wu, Jingyou Yu, Ai-ris Y. Collier, Dan H. Barouch
Summary: This study demonstrates that cellular immunity induced by current SARS-CoV-2 vaccines is highly conserved to the Omicron spike protein. Individuals vaccinated with Ad26.COV2.S or BNT162b2 vaccines showed durable spike-specific CD8(+) and CD4(+) T cell responses that were cross-reactive to both the Delta and Omicron variants, including in central and effector memory cellular subpopulations.
Article
Biochemistry & Molecular Biology
Daniel Y. Zhu, Matthew J. Gorman, Dansu Yuan, Jingyou Yu, Noe B. Mercado, Katherine McMahan, Erica N. Borducchi, Michelle Lifton, Jinyan Liu, Felix Nampanya, Shivani Patel, Lauren Peter, Lisa H. Tostanoski, Laurent Pessaint, Alex Van Ry, Brad Finneyfrock, Jason Velasco, Elyse Teow, Renita Brown, Anthony Cook, Hanne Andersen, Mark G. Lewis, Douglas A. Lauffenburger, Dan H. Barouch, Galit Alter
Summary: This study examines the role of neutralizing antibodies, Fc effector function, and T-cell immunity against SARS-CoV-2 infection. The results indicate that neutralizing antibodies and Fc receptor binding titers are linked to prevention of transmission, while Fc receptor binding/function and T cells are associated with antiviral control. This highlights the importance of Fc effector function as a correlate of immunity in halting and controlling SARS-CoV-2 and emerging variants.
Article
Microbiology
Malika Aid, Samuel J. Vidal, Cesar Piedra-Mora, Sarah Ducat, Chi N. Chan, Stephen Bondoc, Alessandro Colarusso, Carly E. Starke, Michael Nekorchuk, Kathleen Busman-Sahay, Jacob D. Estes, Amanda J. Martinot, Dan H. Barouch
Summary: This study demonstrates the protective effect of Ad26.COV2.S vaccination against SARS-CoV-2 in hamsters and rhesus macaques by preventing excessive immune and coagulation responses. It provides insights into the molecular mechanisms of Ad26.COV2.S vaccine protection against SARS-CoV-2.
Article
Immunology
Daniel J. Stieh, Dan H. Barouch, Christy Comeaux, Michal Sarnecki, Kathryn E. Stephenson, Stephen R. Walsh, Sheetal Sawant, Jack Heptinstall, Georgia D. Tomaras, James G. Kublin, M. Juliana McElrath, Kristen W. Cohen, Stephen C. De Rosa, Galit Alter, Guido Ferrari, David Montefiori, Philipp Mann, Steven Nijs, Katleen Callewaert, Paul A. Goepfert, Srilatha Edupuganti, Etienne Karita, Michael S. Seaman, Lawrence Corey, Lindsey R. Baden, Maria G. Pau, Hanneke Schuitemaker, Frank Tomaka
Summary: This study developed a cross-clade, globally effective HIV vaccine through clinical trials on healthy individuals with low risk for HIV infection. The findings showed that adding mosaic gp140 to the vaccine regimen increased and broadened the elicited immune response without compromising safety or clade C responses.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Letter
Medicine, General & Internal
Ai-ris Y. Collier, Jessica Miller, Nicole P. Hachmann, Katherine McMahan, Jinyan Liu, Esther A. Bondzie, Lydia Gallup, Marjorie Rowe, Eleanor Schonberg, Siline Thai, Julia Barrett, Erica N. Borducchi, Emily Bouffard, Catherine Jacob-Dolan, Camille R. Mazurek, Audrey Mutoni, Olivia Powers, Michaela Sciacca, Nehalee Surve, Haley VanWyk, Cindy Wu, Dan H. Barouch
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Letter
Medicine, General & Internal
Jessica Miller, Nicole P. Hachmann, Ai-ris Y. Collier, Ninaad Lasrado, Camille R. Mazurek, Robert C. Patio, Olivia Powers, Nehalee Surve, James Theiler, Bette Korber, Dan H. Barouch
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Cell Biology
Amanda Cooper, Adam Sidaway, Abishek Chandrashekar, Elizabeth Latta, Krishnendu Chakraborty, Jingyou Yu, Katherine McMahan, Victoria Giffin, Cordelia Manickam, Kyle Kroll, Matthew Mosher, R. Keith Reeves, Rihab Gam, Elisa Arthofer, Modassir Choudhry, Tom Henley, Dan H. Barouch
Summary: Despite the rapid clinical translation of COVID-19 vaccines, there is still an opportunity for vaccine technology innovation to address current limitations and future pandemics. Researchers have developed a universal vaccine cell (UVC) that mimics the natural immune response to viral infection. In animal models and vaccinated individuals, this cellular vaccine has shown the ability to induce robust neutralizing antibodies and provide protection against viral variants.
CELL REPORTS MEDICINE
(2022)
Article
Multidisciplinary Sciences
Jennifer Cable, Barney S. Graham, Richard A. Koup, Robert A. Seder, Katalin Kariko, Norbert Pardi, Dan H. Barouch, Bhawna Sharma, Susanne Rauch, Raffael Nachbagauer, Mattias N. E. Forsell, Michael Schotsaert, Ali H. Ellebedy, Karin Lore, Darrell J. Irvine, Emily Pilkington, Siri Tahtinen, Elizabeth A. Thompson, Yanis Feraoun, Neil P. King, Kevin Saunders, Galit Alter, Syed M. Moin, Kwinten Sliepen, Gunilla B. Karlsson Hedestam, Hedda Wardemann, Bali Pulendran, Nicole A. Doria-Rose, Wan-Ting He, Jennifer A. Juno, Sila Ataca, Adam K. Wheatley, Jason S. McLellan, Laura M. Walker, Julia Lederhofer, Lisa C. Lindesmith, Holger Wille, Peter J. Hotez, Linda-Gail Bekker
Summary: The COVID-19 pandemic has highlighted the importance of vaccines in public health and advancements in vaccine technology are vital for preventing infectious diseases. While many diseases still lack effective vaccines, recent developments in fields like immunology and structural biology may lead to breakthroughs in vaccination and enhance preparedness for future pandemics.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Obstetrics & Gynecology
Ai-ris Y. Collier, Anna M. Modest, Ricardo A. Aguayo, Esther A. Bondzie, Shivani Patel, Michele R. Hacker, Dan H. Barouch
Summary: This study aimed to investigate the differences in T cell phenotype and function in uterine intervillous blood (IVB) between normal pregnancy and preeclampsia, and to explore the immunologic basis of preeclampsia. The results showed that preeclampsia was associated with a greater pro-inflammatory cytokine ratio in uterine IVB T cell subsets, indicating an inflammation-related mechanism of preeclampsia. Therefore, IVB sampling is a useful tool for studying human uterine T cell biology and may provide insights for immunotherapeutic strategies for preeclampsia.
REPRODUCTIVE SCIENCES
(2023)
Correction
Immunology
Etsuro Nanishi, Francesco Borriello, Hyuk-Soo Seo, Timothy R. O'Meara, Marisa E. McGrath, Yoshine Saito, Jing Chen, Joann Diray-Arce, Kijun Song, Andrew Z. Xu, Soumik Barman, Manisha Menon, Danica Dong, Timothy M. Caradonna, Jared Feldman, Blake M. Hauser, Aaron G. Schmidt, Lindsey R. Baden, Robert K. Ernst, Carly Dillen, Jingyou Yu, Aiquan Chang, Luuk Hilgers, Peter Paul Platenburg, Sirano Dhe-Paganon, Dan H. Barouch, Al Ozonoff, Ivan Zanoni, Matthew B. Frieman, David J. Dowling, Ofer Levy
Article
Immunology
Etsuro Nanishi, Francesco Borriello, Hyuk-Soo Seo, Timothy R. O'Meara, Marisa E. McGrath, Yoshine Saito, Jing Chen, Joann Diray-Arce, Kijun Song, Andrew Z. Xu, Soumik Barman, Manisha Menon, Danica Dong, Timothy M. Caradonna, Jared Feldman, Blake M. Hauser, Aaron G. Schmidt, Lindsey R. Baden, Robert K. Ernst, Carly Dillen, Jingyou Yu, Aiquan Chang, Luuk Hilgers, Peter Paul Platenburg, Sirano Dhe-Paganon, Dan H. Barouch, Al Ozonoff, Ivan Zanoni, Matthew B. Frieman, David J. Dowling, Ofer Levy
Summary: The development of vaccines that protect vulnerable populations from SARS-CoV-2 is a public health priority. This study tested different adjuvants and SARS-CoV-2 antigens to identify a combination that induces antibodies and protection in both young and aged mice. An oil-in-water emulsion containing carbohydrate fatty acid monosulphate derivative (CMS:O/W) was found to be the most effective in enhancing immune response and protection across age groups.
Article
Multidisciplinary Sciences
Samuel J. Vidal, Daniel Sellers, Jingyou Yu, Shoko Wakabayashi, Jaimie Sixsmith, Malika Aid, Julia Barrett, Sage F. Stevens, Xiaowen Li, Wenjun Li, Courtney R. Plumlee, Kevin B. Urdahl, Amanda J. Martinot, Dan H. Barouch
Summary: This study found that the live attenuated Mycobacterium tuberculosis vaccine Delta LprG provided better protection compared to BCG in a low-dose murine aerosol challenge model, preventing infection establishment and dissemination and confining the infection to one lung. The protection was partially influenced by certain cytokines.
Article
Cell Biology
Jingyou Yu, Paul V. Thomas, Michaela Sciacca, Cindy Wu, Jinyan Liu, Xuan He, Jessica Miller, Nicole P. Hachmann, Nehalee Surve, Katherine McMahan, Catherine Jacob-Dolan, Olivia Powers, Kevin Hall, Julia Barrett, David Hope, Camille R. Mazurek, Tetyana Murdza, William C. Chang, Emily Golub, Phyllis A. Rees, Caroline E. Peterson, Agnes Hajduczki, Wei-Hung Chen, Elizabeth J. Martinez, Elizabeth Hussin, Camille Lange, Hua Gong, Gary R. Matyas, Mangala Rao, Mehul Suthar, Mona Boursiquot, Anthony Cook, Laurent Pessaint, Mark G. Lewis, Hanne Andersen, Diane L. Bolton, Nelson L. Michael, M. Gordon Joyce, Kayvon Modjarrad, Dan H. Barouch
Summary: SARS-CoV-2 vaccines have reduced protection against the acquisition of the BA.5 subvariant, but remain effective against severe disease. The immune correlates of protection against BA.5 are unknown. This study demonstrates that both homologous and heterologous regimens involving Ad26.COV2.S and SpFN vaccines provide robust protection against a mismatched BA.5 challenge in macaques.
CELL REPORTS MEDICINE
(2023)
Article
Cell Biology
Malika Aid, Alessandro Colarusso, Victoria Walker-Sperling, Dan H. Barouch
Summary: The discovery of biomarkers that predict viral rebound after discontinuation of antiretroviral therapy (ART) would significantly contribute to the HIV cure field.
CELL REPORTS MEDICINE
(2023)