Article
Immunology
Catarina E. Hioe, Xiaomei Liu, Andrew N. Banin, Daniel W. Heindel, Jeromine Klingler, Priyanka G. Rao, Christina C. Luo, Xunqing Jiang, Shilpi Pandey, Tracy Ordonez, Philip Barnette, Maxim Totrov, Jiang Zhu, Arthur Nadas, Susan Zolla-Pazner, Chitra Upadhyay, Xiaoying Shen, Xiang-Peng Kong, Ann J. Hessell
Summary: This study tested a vaccine targeting neutralizing epitopes on the HIV-1 envelope and found that it could induce neutralizing antibody activity in rabbits.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Virology
Salvatore Dimonte, Lavinia Fabeni, Michele Pellegrino, Stefano Aquaro
Summary: This study revealed the close relationship between synonymous mutations associated with HIV-1 tropism and RNA secondary-structure, with some mutations positively related to CCR5 and CXCR4 receptors. These mutations may have an impact on viral RNA stability and therapeutic strategies.
Article
Immunology
Kwinten Sliepen, Edith Schermer, Ilja Bontjer, Judith A. Burger, Reka Felfodine Levai, Philipp Mundsperger, Philip J. M. Brouwer, Monica Tolazzi, Atilla Farsang, Dietmar Katinger, John P. Moore, Gabriella Scarlatti, Robin J. Shattock, Quentin J. Sattentau, Rogier W. Sanders
Summary: The study showed that ISCOMATRIX was the most effective adjuvant, while GLA-LSQ adjuvant unexpectedly induced strong antibody response, though it may compromise the production of more desired anti-trimer antibodies due to an off-target effect. Both adjuvants and nanoparticle display can enhance the antibody response to SOSIP trimers, but the optimal combination requires experimental identification.
Article
Medicine, General & Internal
Glenda E. Gray, Linda-Gail Bekker, Fatima Laher, Mookho Malahleha, Mary Allen, Zoe Moodie, Nicole Grunenberg, Yunda Huang, Doug Grove, Brittany Prigmore, Jia J. Kee, David Benkeser, John Hural, Craig Innes, Erica Lazarus, Graeme Meintjes, Nivashnee Naicker, Dishiki Kalonji, Maphoshane Nchabeleng, Modulakgotla Sebe, Nishanta Singh, Philip Kotze, Sheetal Kassim, Thozama Dubula, Vimla Naicker, William Brumskine, Cleon N. Ncayiya, Amy M. Ward, Nigel Garrett, Girisha Kistnasami, Zakir Gaffoor, Pearl Selepe, Philisiwe B. Makhoba, Matsontso P. Mathebula, Pamela Mda, Tania Adonis, Katlego S. Mapetla, Bontle Modibedi, Tricia Philip, Gladys Kobane, Carter Bentley, Shelly Ramirez, Simbarashe Takuva, Megan Jones, Mpho Sikhosana, Millicent Atujuna, Michele Andrasik, Nima S. Hejazi, Adrian Puren, Lubbe Wiesner, Sanjay Phogat, Carlos Diaz Granados, Marguerite Koutsoukos, Olivier van der Meeren, Susan W. Barnett, Niranjan Kanesa-Thasan, James G. Kublin, M. Juliana McElrath, Peter B. Gilbert, Holly Janes, Lawrence Corey
Summary: The ALVAC-gp120 vaccine regimen did not prevent HIV-1 infection among participants in South Africa, despite previous evidence of immunogenicity. This phase 2b-3 trial showed that further vaccinations were halted due to lack of efficacy in preventing HIV-1 infection.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Review
Immunology
Alicja Maria Chmielewska, Anna Czarnota, Krystyna Bienkowska-Szewczyk, Katarzyna Grzyb
Summary: This article discusses the background of the COVID-19 pandemic, the development of vaccines, and concerns about virus variants. It also evaluates common experimental methods used to test neutralizing antibody responses against SARS-CoV-2 variants. In addition, recent studies on the immune responses elicited by available vaccines against major SARS-CoV-2 variants are briefly reviewed.
Article
Virology
Daniel P. Leaman, Armando Stano, Yajing Chen, Lei Zhang, Michael B. Zwick
Summary: The study introduces a novel multivalent mEnv vaccine platform called MELs, which does not require protein engineering or extraneous proteins. Through a sequential immunization scheme in rabbits, MELs were able to elicit antibodies that neutralized tier 2 HIV isolates.
JOURNAL OF VIROLOGY
(2021)
Article
Medicine, General & Internal
Line Dam Heftdal, Andreas Dehlbaek Knudsen, Sebastian Rask Hamm, Cecilie Bo Hansen, Dina Leth Moller, Mia Pries-Heje, Kamille Fogh, Rasmus Bo Hasselbalch, Ida Jarlhelt, Laura Perez-Alos, Linda Maria Hilsted, Sisse Rye Ostrowski, Jan Gerstoft, Kirsten Gronbaek, Henning Bundgaard, Kasper Iversen, Peter Garred, Susanne Dam Nielsen
Summary: This study found reduced IgG antibody response to the BNT162b2 vaccine in people with HIV, highlighting the need for increased awareness of breakthrough infections in this population.
JOURNAL OF INTERNAL MEDICINE
(2022)
Article
Virology
Santhi Devasundaram, Margherita Rosati, Antonio Valentin, Svenja Weiss, Vincenza Itri, Hung V. Trinh, Jenifer Bear, Bhabadeb Chowdhury, Celia C. LaBranche, David Montefiori, Guido Ferrari, Mangala Rao, Xiang-Peng Kong, Susan Zolla-Pazner, George N. Pavlakis, Barbara K. Felber
Summary: Priming with DNA expressing the trimeric V1V2 scaffold alters the hierarchy of humoral immune responses to V2 region epitopes, providing a method for more efficient induction and maintenance of V2-specific Env Abs associated with reduced risk of HIV infection. This work demonstrates that focusing immune responses on the V1V2 region through DNA priming vaccination induces improved recognition of epitopes important for protective immunity, particularly V2-specific humoral immune responses inversely correlating with HIV risk of infection in the RV144 trial.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xinling Wang, Miao Cao, Yanling Wu, Wei Xu, Qian Wang, Tianlei Ying, Lu Lu, Shibo Jiang
Summary: Despite the progress made with HAART therapy, challenges remain for the treatment of HIV-1 virus. Studies have shown that combining a gp120 binding protein and a gp41 binding antibody may have a synergistic effect in inhibiting the spread of HIV-1.
Article
Immunology
Daniele Lapa, Daria M. Grousova, Giulia Matusali, Silvia Meschi, Francesca Colavita, Aurora Bettini, Giulia Gramigna, Massimo Francalancia, Anna Rosa Garbuglia, Enrico Girardi, Vincenzo Puro, Andrea Antinori, Anna Kovyrshina, Inna Dolzhikova, Dmitry Shcheblyakov, Amir Tukhvatulin, Olga Zubkova, Vladimir A. Gushchin, Denis Y. Logunov, Boris S. Naroditsky, Francesco Vaia, Alexander L. Gintsburg
Summary: The Omicron variant of SARS-CoV-2 is rapidly spreading worldwide and has become dominant, leading to varying degrees of decreased neutralizing antibodies in vaccinated and infected individuals, highlighting the necessity of a third booster vaccination.
Article
Biochemistry & Molecular Biology
Ye Sang, Zhen Zhang, Fan Liu, Haitao Lu, Changxiao Yu, Huisheng Sun, Jinrong Long, Yiming Cao, Jierui Mai, Yiqi Miao, Xin Wang, Jiaxin Fang, Youchun Wang, Weijin Huang, Jing Yang, Shengqi Wang
Summary: Monkeypox has been declared a public health emergency by the World Health Organization. Two mRNA vaccines, mRNA-A-LNP and mRNA-B-LNP, based on specific proteins of the monkeypox virus, have been developed and shown to induce immune responses in mice, including specific antibodies and cellular immunity. These vaccines also provide protection against vaccinia virus challenge in mice and have the potential to be used against other orthopoxviruses.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
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
Microbiology
Safia S. Aljedani, Tyler J. Liban, Karen Tran, Ganesh Phad, Suruchi Singh, Viktoriya Dubrovskaya, Pradeepa Pushparaj, Paola Martinez-Murillo, Justas Rodarte, Alex Mileant, Vidya Mangala Prasad, Rachel Kinzelman, Sijy O'Dell, John R. Mascola, Kelly K. Lee, Gunilla B. Karlsson Hedestam, Richard T. Wyatt, Marie Pancera
Summary: Understanding how antibodies target and neutralize specific regions of the HIV-1 envelope glycoprotein is crucial for vaccine development. Structural analysis revealed that vaccine-induced antibodies from different clonal lineages can penetrate the glycan shield to recognize a unique region within the V2 area, leading to potent neutralization of the autologous virus.
Article
Biochemistry & Molecular Biology
Anju Krishnan Anitha, Pratibha Narayanan, Neethu Ajayakumar, Krishnankutty Chandrika Sivakumar, Kesavakurup Santhosh Kumar
Summary: This study designed and generated peptide ligands targeting CCR5, which showed significant CCR5 specificity and did not mediate migration of responsive cells.
JOURNAL OF BIOCHEMISTRY
(2022)
Article
Immunology
Sebastian Slomka, Patrycja Zieba, Oskar Rosiak, Anna Piekarska
Summary: This study conducted a long-term analysis of the immune response in individuals vaccinated with two types of COVID-19 vaccines. The mRNA vaccine group exhibited a stronger immune response with higher levels of IgG antibodies and neutralizing antibodies compared to the vector vaccine group, regardless of previous SARS-CoV-2 infection.
Article
Virology
Santhi Devasundaram, Margherita Rosati, Antonio Valentin, Svenja Weiss, Vincenza Itri, Hung V. Trinh, Jenifer Bear, Bhabadeb Chowdhury, Celia C. LaBranche, David Montefiori, Guido Ferrari, Mangala Rao, Xiang-Peng Kong, Susan Zolla-Pazner, George N. Pavlakis, Barbara K. Felber
Summary: Priming with DNA expressing the trimeric V1V2 scaffold alters the hierarchy of humoral immune responses to V2 region epitopes, providing a method for more efficient induction and maintenance of V2-specific Env Abs associated with reduced risk of HIV infection. This work demonstrates that focusing immune responses on the V1V2 region through DNA priming vaccination induces improved recognition of epitopes important for protective immunity, particularly V2-specific humoral immune responses inversely correlating with HIV risk of infection in the RV144 trial.
JOURNAL OF VIROLOGY
(2021)
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
Jeromine Klingler, Svenja Weiss, Vincenza Itri, Xiaomei Liu, Kasopefoluwa Y. Oguntuyo, Christian Stevens, Satoshi Ikegame, Chuan-Tien Hung, Gospel Enyindah-Asonye, Fatima Amanat, Ian Baine, Suzanne Arinsburg, Juan C. Bandres, Erna Milunka Kojic, Jonathan Stoever, Denise Jurczyszak, Maria Bermudez-Gonzalez, Arthur Nadas, Sean Liu, Benhur Lee, Susan Zolla-Pazner, Catarina E. Hioe
Summary: The study found that spike- and RBD-specific IgM, IgG1, and IgA1 were produced by all or nearly all individuals in convalescent plasma, with these immunoglobulins playing critical roles in neutralizing the virus.
JOURNAL OF INFECTIOUS DISEASES
(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
Biochemistry & Molecular Biology
Ian Miller, Max Totrov, Lioubov Korotchkina, Denis N. Kazyulkin, Andrei Gudkov, Sergey Korolev
Summary: Research on L1-EN has revealed that its sequence specificity and catalytic activity are influenced by the conformational properties of the preferred sequence. Unlike other nucleases, L1-EN does not bend the DNA helix, but rather causes 'compression' near the cleavage site, providing multiple advantages for retrotransposition. This work could potentially lead to the development of L1-EN inhibitors as anti-cancer and anti-aging therapeutics.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Microbiology
Olga Lomovskaya, Ruslan Tsivkovski, Dongxu Sun, Raja Reddy, Maxim Totrov, Scott Hecker, David Griffith, Jeffery Loutit, Michael Dudley
Summary: QPX7728 is an ultra-broad-spectrum beta-lactamase inhibitor with potent inhibition against a wide range of clinically important beta-lactamases. It is minimally affected by common resistance mechanisms and shows broad coverage when combined with various beta-lactam antibiotics. The oral delivery option of QPX7728 also provides potential for application in combination products.
FRONTIERS IN MICROBIOLOGY
(2021)
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
Chemistry, Medicinal
Hanan Almolhim, Sha Ding, Joshua H. Butler, Emily K. Bremers, Grant J. Butschek, Carla Slebodnick, Emilio F. Merino, Zaira Rizopoulos, Maxim Totrov, Maria B. Cassera, Paul R. Carlier
Summary: The tetrahydro-beta-carboline scaffold is a promising structure for the discovery of antimalarial agents. The molecule N2-acyl tetrahydro-beta-carboline GNFP-f-5009 ((+/-)-3b) was found through similarity searching and showed in vitro efficacy against P. falciparum. The enantiomer (R)-3b demonstrated superior pharmacological properties. However, oral efficacy was lacking in mouse testing, possibly due to unfavorable physicochemical properties.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Jopaul Mathew, Sha Ding, Kevin A. Kunz, Emily E. Stacy, Joshua H. Butler, Reagan S. Haney, Emilio F. Merino, Grant J. Butschek, Zaira Rizopoulos, Maxim Totrov, Maria B. Cassera, Paul R. Carlier
Summary: Virtual ligand screening using a pharmacophore derived from antimalarial MMV008138 led to the identification of TCMDC-140230 as a compound worth exploring. However, none of the four stereoisomers synthesized showed potent inhibition of Plasmodium falciparum growth, while a minor byproduct 7e exhibited strong in vitro antimalarial activity and was orally efficacious in an in vivo mouse model of malaria.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Eugene Raush, Ruben Abagyan, Maxim Totrov
Summary: This paper presents a GCNN-based method for learning and predicting statistical torsional profiles in small organic molecules. By training a specialized GCNN model, it accurately captures various torsional preferences and shows good agreement with quantum chemistry calculations. The application of this method in conformer generation further demonstrates its potential value.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Virology
Zhi Yang, Kim-Marie A. Dam, Jonathan M. Gershoni, Susan Zolla-Pazner, Pamela J. Bjorkman
Summary: The RV144 HIV-1 clinical vaccination trial showed modest protection against viral infection. Antibody responses to the V1V2 region of HIV-1 Env gp120 were correlated inversely with the risk of infection, and data from three other clinical vaccine trials suggested a similar signal. In this study, V2i antibodies and CD4i antibody CG10 were characterized for their interactions with open Env trimers bound to CD4. The findings provide insights into the immune mechanisms during HIV-1 infection.
JOURNAL OF VIROLOGY
(2022)