Article
Virology
Saori Matsuoka, Takeo Kuwata, Hiroshi Ishii, Tsuyoshi Sekizuka, Makoto Kuroda, Masato Sano, Midori Okazaki, Hiroyuki Yamamoto, Mikiko Shimizu, Shuzo Matsushita, Yohei Seki, Akatsuki Saito, Hiromi Sakawaki, Vanessa M. Hirsch, Tomoyuki Miura, Hirofumi Akari, Tetsuro Matano
Summary: This study found a potent antibody induction associated with germ line BCR/antibody Ig gene polymorphism in rhesus macaques infected with SIV. The results demonstrate that a single nucleotide polymorphism in germ line Ig genes could be a determinant for induction of potent antibodies against virus infection. Germ line BCR/antibody Ig gene polymorphisms may be a factor restricting effective antibody induction or responsiveness to vaccination.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Widade Ziani, Anya Bauer, Hong Lu, Xiaolei Wang, Xueling Wu, Katharine J. Bar, Hui Li, Dongfang Liu, George M. Shaw, Ronald S. Veazey, Huanbin Xu
Summary: The newly developed SHIV.C.CH848 can establish sustained viremia and viral reservoirs in rhesus macaques with clinical immunodeficiency consequences, providing a valuable SHIV model for HIV research. The findings suggest that this CCR5-tropic, SHIVC strain is valuable for testing responses to HIV vaccines and therapeutics in nonhuman primate models.
JOURNAL OF VIROLOGY
(2021)
Article
Cell Biology
Nongthombam Boby, Alyssa Ransom, Barcley T. Pace, Kelsey M. Williams, Christopher Mabee, Arpita Das, Sudesh K. Srivastav, Edith Porter, Bapi Pahar
Summary: Increased production of TGF-beta was observed in intestinal CD3(-)CD20(-)CD68(+) cells from SIV-infected rhesus macaques, which negatively correlated with the frequency of jejunum CD4(+) T cells. Disruption of a negative feedback loop mediated by SMAD7 may enhance TGF-beta production and SMAD-dependent signaling in SIV infection.
Article
Immunology
Sanghita Sarkar, David A. Spencer, Philip Barnette, Shilpi Pandey, William F. Sutton, Madhubanti Basu, Reuben E. Burch, John D. Cleveland, Alexander F. Rosenberg, Javier Rangel-Moreno, Michael C. Keefer, Ann J. Hessell, Nancy L. Haigwood, James J. Kobie
Summary: The study found that HIV neutralizing antibodies were still generated even in the absence of CD4+ T cell help, and the effectiveness of HIV vaccine may still exist in the presence of diminished CD4+ T cell help.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Roslyn A. Taylor, Michael D. McRaven, Ann M. Carias, Meegan R. Anderson, Edgar Matias, Mariluz Arainga, Edward J. Allen, Kenneth A. Rogers, Sandeep Gupta, Viraj Kulkarni, Samir Lakhashe, Ramon Lorenzo-Redondo, Yanique Thomas, Amanda Strickland, Francois J. Villinger, Ruth M. Ruprecht, Thomas J. Hope
Summary: The study showed that HIV rapidly spread and penetrated the entire gastrointestinal tract in neonatal rhesus macaques as early as four hours after oral viral challenge, with the largest number of infected cells found in the small and large intestine at 96 hours, predominantly T cells. These findings highlight the importance of understanding viral distribution and infection dynamics in neonates.
Article
Immunology
Mark Chernyshev, Mateusz Kaduk, Martin Corcoran, Gunilla B. Karlsson Hedestam
Summary: This study quantified VDJ gene usage levels in the unmutated IgM repertoires of 45 macaques, revealing similar patterns of gene usage among macaque subgroups and individuals. Unlike humans, macaques showed a higher usage of IGHV4 family genes and evidence of evolutionary expansion of this gene family.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Ines Frank, Mariasole Cigoli, Muhammad S. Arif, Marissa D. Fahlberg, Stephanie Maldonado, Giulia Calenda, Amarendra Pegu, Eun Sung Yang, Reda Rawi, Gwo-Yu Chuang, Hui Geng, Cuiping Liu, Tongqing Zhou, Peter D. Kwong, James Arthos, Claudia Cicala, Brooke F. Grasperge, James L. Blanchard, Agegnehu Gettie, Christine M. Fennessey, Brandon F. Keele, Monica Vaccari, Thomas J. Hope, Anthony S. Fauci, John R. Mascola, Elena Martinelli
Summary: In this study, it was found that combining bNAbs with Rh-α(4)β(7) integrin blockade delayed viral rebound in SHIVSF162P3-infected macaques compared to treatment with bNAbs alone. The combination therapy showed a modest prolongation of virologic control in some macaques, indicating the potential benefit of targeting both bNAbs and integrin alpha(4)beta(7) in antiviral therapy.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Immunology
Kevin S. White, Joshua A. Walker, John Wang, Patrick Autissier, Andrew D. Miller, Nadia N. Abuelezan, Rachel Burrack, Qingsheng Li, Woong-Ki Kim, Kenneth C. Williams
Summary: Despite effective antiretroviral therapy, comorbidities such as neurocognitive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. This study investigates the co-development of cardiac pathology and CNS pathology in SIV-infected rhesus macaques, demonstrating a strong correlation with activated myeloid cells. Similar observations were confirmed in HIV-infected individuals, highlighting the need for adjunctive therapies targeting macrophages.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
David A. Garber, Patricia Guenthner, James Mitchell, Shanon Ellis, Anna Gazumyan, Martha Nason, Michael S. Seaman, Janet M. McNicholl, Michel C. Nussenzweig, Walid Heneine
Summary: The study demonstrated significant protection against repeated intravenous SHIV challenges with broadly neutralizing antibodies, particularly 10-1074. In the experiment, 10-1074 showed relatively longer persistence in vivo, while the levels of 3BNC117 were undetectable.
Article
Immunology
Dan Liu, Jiaojiao Liu, Tingting Xu, Hongwei Qiao, Yu Qi, Yuxun Gao, Ailixire, Lei Gao, Chunlin Li, Mingrui Xia, Hongjun Li
Summary: Using SIV-infected macaques as a model, this study found brain volume changes at 12 weeks post-infection in various brain regions. Despite early initiation of cART after SIV infection, brain atrophy in macaques was still observed, with signs of potential reversibility. Plasma viral load was associated with subcortical nucleus volume, while CD4(+) T-cell count and CD4(+)/CD8(+) ratio in plasma were linked to widespread cortical volume changes.
Article
Medicine, Research & Experimental
Benjamin D. Varco-Merth, William Brantley, Alejandra Marenco, Derick D. Duell, Devin N. Fachko, Brian Richardson, Kathleen Busman-Sahay, Danica Shao, Walter Flores, Kathleen Engelman, Yoshinori Fukazawa, Scott W. Wong, Rebecca L. Skalsky, Jeremy Smedley, Michael K. Axthelm, Jeffrey D. Lifson, Jacob D. Estes, Paul T. Edlefsen, Louis J. Picker, Cheryl M. A. Cameron, Timothy J. Henrich, Afam A. Okoye
Summary: Inhibiting mTOR can decrease the proliferation of CD4(+)TM cells, but chronic mTOR inhibition alone or in combination with T cell activation is not sufficient to disrupt the stability of the SIV reservoir.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Cell Biology
Bhavna Hora, Hui Li, Xiaoying Shen, Mitchell Martin, Yue Chen, Madison Berry, Tyler Evangelous, Andrew N. Macintyre, Aria Arus-Altuz, Shuyi Wang, Ajay Singh, Chengyan Zhao, Nicole De Naeyer, Todd DeMarco, Cindy Kuykendall, Thaddeus Gurley, Kevin O. Saunders, Thomas Denny, M. Anthony Moody, John Misamore, Mark G. Lewis, Kevin Wiehe, Derek W. Cain, David C. Montefiori, George M. Shaw, Wilton B. Williams
Summary: A neonatal model for the induction of heterologous HIV-1 nAbs was established in infected rhesus macaques, showing the development of potent and polyclonal heterologous nAbs over time.
Article
Medicine, Research & Experimental
Peng Xiao, Sanjeev Gumber, Mark A. Marzinke, Thuy Hoang, Rohan Myers, Abhijit A. Date, Justin Hanes, Laura M. Ensign, Lin Wang, Lisa C. Rohan, Richard Cone, Edward J. Fuchs, Craig W. Hendrix, Francois Villinger
Summary: In rural areas, the rate of new HIV infections is higher among men having sex with men (MSM), with limited access to PrEP. A study has optimized and tested rectal douches and found that HOsm douching provides better protection against virus acquisition, serving as a potential low-cost and safe alternative to PrEP.
Article
Virology
Catherine Jacob-Dolan, Jared Feldman, Katherine McMahan, Jingyou Yu, Roland Zahn, Frank Wegmann, Hanneke Schuitemaker, Aaron G. Schmidt, Dan H. Barouch
Summary: This study defines the serum profiles in rhesus macaques after SARS-CoV-2 vaccination, showing robust reactivity to SARS-CoV-2 spike protein but reduced cross reactivity to other coronaviruses. Neutralizing antibody responses were predominantly SARS-CoV-2 specific, highlighting the similarities between infection and vaccine-induced immunity for SARS-CoV-2.
JOURNAL OF VIROLOGY
(2021)
Article
Microbiology
Anya Bauer, Emily Lindemuth, Francesco Elia Marino, Ryan F. Krause, Jaimy Joy, Steffen P. Docken, Suvadip Mallick, Kevin M. McCormick, Clinton J. Holt, Ivelin A. Georgiev, Barbara C. Felber, Brandon A. Keele, Ronald C. Veazey, Miles A. Davenport, Hui C. Li, George A. Shaw, Katharine C. Bar
Summary: This study reported the generation of a minimally adapted virus, SHIV.C.CH505.v2, which has enhanced replication fitness and preserved native Env properties. It can be used as a new reagent for nonhuman primate studies of HIV-1 transmission, pathogenesis, and cure.
Article
Immunology
David A. Spencer, Delphine C. Malherbe, Nestor Vazquez Bernat, Monika Adori, Benjamin Goldberg, Nicholas Dambrauskas, Heidi Henderson, Shilpi Pandey, Tracy Cheever, Philip Barnette, William F. Sutton, Margaret E. Ackerman, James J. Kobie, D. Noah Sather, Gunilla B. Karlsson Hedestam, Nancy L. Haigwood, Ann J. Hessell
Summary: Efforts to combat HIV are hindered by viral diversity and shielding of neutralization epitopes, but this study shows potential for eliciting protective Abs through vaccination, with some mAbs demonstrating neutralizing activity.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Ann J. Hessell, Liuzhe Li, Delphine C. Malherbe, Philip Barnette, Shilpi Pandey, William Sutton, David Spencer, Xiao-Hong Wang, Johannes S. Gach, Ruth Hunegnaw, Michael Tuen, Xunqing Jiang, Christina C. Luo, Celia C. LaBranche, Yongzhao Shao, David C. Montefiori, Donald N. Forthal, Ralf Duerr, Marjorie Robert-Guroff, Nancy L. Haigwood, Miroslaw K. Gorny
Summary: The study tested the role of vaccine-induced anti-V2 antibodies in protecting rhesus macaques from SHIV infection. The results showed that while vaccine-induced neutralizing and nonneutralizing antibodies played a role in controlling viral loads, nonneutralizing V2 antibodies alone may not be sufficient to control the virus.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Delphine C. Malherbe, Lo Vang, Jason Mendy, Philip T. Barnette, David A. Spencer, Jason Reed, Bettie W. Kareko, D. Noah Sather, Shilpi Pandey, Constantinos K. Wibmer, Harlan Robins, Deborah H. Fuller, Byung Park, Samir K. Lakhashe, James M. Wilson, Michael K. Axthelm, Ruth M. Ruprecht, Penny L. Moore, Jonah B. Sacha, Ann J. Hessell, Jeff Alexander, Nancy L. Haigwood
Summary: A comparative vaccine challenge study in rhesus macaques showed that the combination vaccination with SAd7+Protein was superior in reducing viral seeding in tissues. Despite the lack of protection from infection, the higher antibody responses elicited in this vaccine group may help limit tissue viral seeding.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Nichole R. Klatt, Courtney Broedlow, Jessica M. Osborn, Andrew T. Gustin, Sandra Dross, Megan A. O'Connor, Ernesto Coronado, Philip Barnette, Tiffany Hensley-McBain, Alexander S. Zevin, Roshell Muir, Alexander Roederer, Solomon Wangari, Naoto Iwayama, Chul Y. Ahrens, Jeremy Smedley, Cassandra Moats, Rebecca M. Lynch, Elias K. Haddad, Nancy L. Haigwood, Deborah H. Fuller, Jennifer A. Manuzak
Summary: Although probiotics were well-tolerated when administered with SIV/HIV vaccination, vaccine-specific responses were not significantly enhanced. Additional work will be necessary to develop more effective strategies of microbiome modulation in order to enhance mucosal vaccine immunogenicity and improve protective immune responses.
Article
Virology
Yvonne J. Rosenberg, Xiaoming Jiang, Tracy Cheever, Felicity J. Coulter, Shilpi Pandey, Markus Sack, Lingjun Mao, Lori Urban, Jonathan Lees, Miranda Fischer, Jeremy Smedley, Heather Sidener, Jeffrey Stanton, Nancy L. Haigwood
Summary: Plant-produced antibodies showed promising results as passive immunoprophylaxis in a breastfeeding model in newborns. The use of human neutralizing antibodies effectively prevented infection in newborn monkeys and offered advantages in cost of production and safety. The findings suggest that anti-Env antibodies may play a role in controlling viral replication in this newborn model.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Liuzhe Li, Ann J. Hessell, Xiang-Peng Kong, Nancy L. Haigwood, Miroslaw K. Gorny
Summary: This study investigated the repertoire of antibodies produced upon vaccination against a particular antigenic site in rhesus macaques. The results showed strong and dynamic antibody responses with multiple immunizations, indicating the potent targeting ability of vaccine-induced immune responses.
Article
Multidisciplinary Sciences
Xiao L. Chang, Gabriela M. Webb, Helen L. Wu, Justin M. Greene, Shaheed Abdulhaqq, Katherine B. Bateman, Jason S. Reed, Cleiton Pessoa, Whitney C. Weber, Nicholas Maier, Glen M. Chew, Roxanne M. Gilbride, Lina Gao, Rebecca Agnor, Travis Giobbi, Jeffrey Torgerson, Don Siess, Nicole Burnett, Miranda Fischer, Oriene Shiel, Cassandra Moats, Bruce Patterson, Kush Dhody, Scott Kelly, Nader Pourhassan, Diogo M. Magnani, Jeremy Smedley, Benjamin N. Bimber, Nancy L. Haigwood, Scott G. Hansen, Timothy R. Brown, Lishomwa C. Ndhlovu, Jonah B. Sacha
Summary: This study demonstrates that competitive inhibition of HIV Env-CCR5 binding with the CCR5-specific antibody Leronlimab can protect rhesus macaques from infection by CCR5-tropic SHIV, suggesting that CCR5 blockade is a promising approach for HIV prophylaxis.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Benjamin S. Goldberg, Chengzi Kaku, Jeremy Dufloo, Timothee Bruel, Olivier Schwartz, David A. Spencer, Ann J. Hessell, Margaret E. Ackerman
Summary: The role of complement system in HIV-1 immunity and pathogenesis is complex, and recent experiments have shown that complement-mediated antibody activities exhibit a high degree of context dependence. Improved understanding of complement activities mediated by HIV-1-specific antibodies has the potential to advance clinical development efforts. Further studies are needed to investigate the role of complement in antibody-mediated prevention of HIV-1 infection by next-generation bnAbs.
Article
Multidisciplinary Sciences
David A. Spencer, Benjamin S. Goldberg, Shilpi Pandey, Tracy Ordonez, Jeremy Dufloo, Philip Barnette, William F. Sutton, Heidi Henderson, Rebecca Agnor, Lina Gao, Timothee Bruel, Olivier Schwartz, Nancy L. Haigwood, Margaret E. Ackerman, Ann J. Hessell
Summary: Antibodies are increasingly used to treat and prevent viral infections. In this study, the researchers investigated the role of antibody-mediated effector and complement activity in protecting against SHIV in rhesus macaques. They found that enhancing complement function did not improve the protective efficacy of the antibody, suggesting that effector functions of the unmodified antibody contribute to its effectiveness.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Svenja Weiss, Vincenza Itri, Ruimin Pan, Xunqing Jiang, Christina C. Luo, Lynn Morris, Delphine C. Malherbe, Philip Barnette, Jeff Alexander, Xiang-Peng Kong, Nancy L. Haigwood, Ann J. Hessell, Ralf Duerr, Susan Zolla-Pazner
Summary: The authors demonstrate that an HIV vaccine targeting the V1V2 region of gp120 is superior to whole envelope vaccines or natural infection in inducing V1V2 antibodies with anti-viral functions that correlate with protection.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Sanghita Sarkar, David A. Spencer, Philip Barnette, Shilpi Pandey, William F. Sutton, Madhubanti Basu, Reuben E. Burch, John D. Cleveland, Alexander F. Rosenberg, Javier Rangel-Moreno, Michael C. Keefer, Ann J. Hessell, Nancy L. Haigwood, James J. Kobie
Summary: The study found that HIV neutralizing antibodies were still generated even in the absence of CD4+ T cell help, and the effectiveness of HIV vaccine may still exist in the presence of diminished CD4+ T cell help.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Marcos D. Petersen, Hugo P. Carignano, Claudia Mongini, Diego Gonzalez, Juan Jaworski
Summary: This study investigated the relative expression of BLV-encoded miRNA blv-miR-b4-3p, host analogous miRNA bo-miR-29a, and potential target mRNAs (HBP-1 and PXDN) in cattle naturally infected with BLV. It was found that PXDN was significantly downregulated in BLV-infected cattle, suggesting the involvement of blv-miR-b4-3p in BLV tumorigenesis.
Article
Multidisciplinary Sciences
Jeremie Prevost, Yaozong Chen, Fei Zhou, William D. Tolbert, Romain Gasser, Halima Medjahed, Manon Nayrac, Dung N. Nguyen, Suneetha Gottumukkala, Ann J. Hessell, Venigalla B. Rao, Edwin Pozharski, Rick K. Huang, Doreen Matthies, Andres Finzi, Marzena Pazgier
Summary: Resistance to the HIV-1 entry inhibitor temsavir is not solely determined by residue 375, but also involves other residues within the gp120 inner domain layers. The resistance is mediated by crosstalk between residue 375 and the inner domain layers. Additionally, temsavir has the ability to adjust its binding mode to accommodate changes in Env conformation, contributing to its broad antiviral activity.
NATURE COMMUNICATIONS
(2023)