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Articles by Galit Alter
Immune genetic associations of antibody Fc-profiles across twins
Abstract Antibodies are bifunctional molecules that play a critical role in immune defense, both through their ability to recognize a near infinite number of targets via gene rearrangement and somatic hypermutation in their antigen-binding (Fab) region, and by directing the functional activity of the immune system via subclass/isotype switching and post-translational modifications of the fragment crystallizable (Fc) region.
Industrial-scale mRNA expertise meets a century of tuberculosis immunology
A protective tuberculosis vaccine is needed. Two mRNA vaccines against Mycobacterium tuberculosis infection exhibit robust immunogenicity and efficacy in rodents. Those same vaccines are currently in clinical trials.
A combination typhoid and non-typhoidal Salmonella polysaccharide conjugate vaccine in healthy adults: a randomized, placebo-controlled phase 1 trial - Nature Medicine
Abstract In sub-Saharan Africa, typhoidal and non-typhoidal Salmonella (NTS) are leading causes of invasive disease among young children. Trivalent Salmonella conjugate vaccine (TSCV) consists of Vi capsule polysaccharide conjugated to tetanus toxoid and core-plus-O-polysaccharides from the two most prevalent invasive NTS serovars conjugated to flagellin subunits. We conducted a first-in-human, randomized, placebo-controlled, phase 1 trial evaluating the safety and immunogenicity of TSCV.
Antibody-Fab and -Fc features promote Mycobacterium tuberculosis restriction
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Keywords Mycobacterium tuberculosis humoral immunity monoclonal antibody Fc effector function opsinophagocytosis alveolar macrophage neutrophil lung immunity Introduction With an estimated 10 million new cases worldwide and approximately 1.6 million associated deaths annually, tuberculosis (TB) remains one of the world’s deadliest infectious diseases.1 Novel drugs, host-directed therapies, and vaccines are needed to combat this global health threat.
By Patricia Grace, Joshua Peters, Jaimie Sixsmith, Richard Lu, Edward B. Irvine, Corinne Luedeman, Brooke A. Fenderson, Andrew J. Vickers, Matthew D. Slein, Tanya R. McKitrick, Mo-Hui Wei, Richard Cummings, Aaron Curtis Wallace, Lisa A. Cavacini, Alok Choudhary, Megan K. Proulx, Christopher Sundling, Gunilla Källenius, Joel D. Ernst, Arturo Casadevall, Camille Locht, Abraham Pinter, Christopher Sassetti, Bryan D Bryson, Sarah Fortune, Galit Alter, Rajko Reljic
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Cell Press
Verified
Anti-dengue virus antibodies that elicit complement-mediated lysis of Zika virion correlate with protection from severe dengue disease
ArticleVolume 44, Issue 5115613Open access 1Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA 2Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA 3Sustainable Sciences Institute, Managua, Nicaragua 4Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA 5Centro de Salud Sócrates Flores Vivas, Ministerio de Salud, Managua, Nicaragua 6Laboratorio Nacional de Virologia,...
Author Correction: Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccines by adjuvanting the ionizable lipid and the mRNA - Nature Biomedical Engineering
Correction to: Nature Biomedical Engineering https://doi.org/10.1038/s41551-023-01082-6, published online 7 September 2023. In the version of this article originally published, an error occurred in the ELISpot images in Fig. 2f. Specifically, the representative image for the left MC3 panel was inadvertently duplicated from the right Lipid 211 panel. The original and corrected versions of Fig. 2f are provided below (Fig. 1).
Fc-engineered antibodies promote neutrophil-dependent control of Mycobacterium tuberculosis - Nature Microbiology
Abstract Mounting evidence indicates that antibodies can contribute towards control of tuberculosis (TB). However, the underlying mechanisms of humoral immune protection and whether antibodies can be exploited in therapeutic strategies to combat TB are relatively understudied. Here we engineered the receptor-binding Fc (fragment crystallizable) region of an antibody recognizing the Mycobacterium tuberculosis (Mtb) capsule, to define antibody Fc-mediated mechanism(s) of Mtb restriction.
Age and sex influence antibody profiles associated with tuberculosis progression - Nature Microbiology
Abstract Antibody features vary with tuberculosis (TB) disease state. Whether clinical variables, such as age or sex, influence associations between Mycobacterium tuberculosis-specific antibody responses and disease state is not well explored. Here we profiled Mycobacterium tuberculosis-specific antibody responses in 140 TB-exposed South African individuals from the Adolescent Cohort Study.
Boosting with adjuvanted SCB-2019 elicits superior Fcγ-receptor engagement driven by IgG3 to SARS-CoV-2 spike - npj Vaccines
Abstract With the continued emergence of variants of concern, the global threat of COVID-19 persists, particularly in low- and middle-income countries with limited vaccine access. Protein-based vaccines, such as SCB-2019, can be produced on a large scale at a low cost while antigen design and adjuvant use can modulate efficacy and safety.
Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccines by adjuvanting the ionizable lipid and the mRNA - Nature Biomedical Engineering
Abstract To elicit optimal immune responses, messenger RNA vaccines require intracellular delivery of the mRNA and the careful use of adjuvants. Here we report a multiply adjuvanted mRNA vaccine consisting of lipid nanoparticles encapsulating an mRNA-encoded antigen, optimized for efficient mRNA delivery and for the enhanced activation of innate and adaptive responses.
Beta-containing bivalent SARS-CoV-2 protein vaccine elicits durable broad neutralization in macaques and protection in hamsters - Communications Medicine
Abstract Background Since the beginning of the COVID-19 pandemic, several variants of concern (VOC) have emerged for which there is evidence of an increase in transmissibility, more severe disease, and/or reduced vaccine effectiveness. Effective COVID-19 vaccine strategies are required to achieve broad protective immunity against current and future VOC.
Author Correction: The persistence of memory: defining, engineering, and measuring vaccine durability - Nature Immunology
Correction to: Nature Immunology https://doi.org/10.1038/s41590-022-01359-z. Published online 1 December 2022. In the version of this article initially published, the name of Ignacio Sanz (Emory University) was incorrectly shown as “Ingancio Sanz” in the second paragraph of the “Measurement of vaccine durability” section. The error has been corrected in the HTML and PDF versions of the article.
The persistence of memory: defining, engineering, and measuring vaccine durability - Nature Immunology
The US National Institute of Allergy and Infectious Diseases (NIAID) convened a virtual workshop in July 2022 to address the research landscape and identify gaps and opportunities in the understanding of durable vaccine protection. The durability of vaccines has been an important global public health issue since the rapid development and deployment of successful vaccines for SARS-CoV-2.
A lab-on-a-chip for the concurrent electrochemical detection of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in saliva and plasma - Nature Biomedical Engineering
Abstract Rapid, accurate and frequent detection of the RNA of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and of serological host antibodies to the virus would facilitate the determination of the immune status of individuals who have Coronavirus disease 2019 (COVID-19), were previously infected by the virus, or were vaccinated against the disease.
Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms - Nature Communications
Abstract The availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing of vaccination in pregnancy impact maternal and neonatal immunity. Here, we characterize the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals and evaluate transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads.
Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae
Abstract The diagnosis and management of post-acute sequelae of COVID-19 (PASC) poses an ongoing medical challenge. Identifying biomarkers associated with PASC would immensely improve the classification of PASC patients and provide the means to evaluate treatment strategies. We analyzed plasma samples collected from a cohort of PASC and COVID-19 patients (n = 63) to quantify circulating viral antigens and inflammatory markers.
The multifaceted roles of breast milk antibodies
Aagaard K. Ma J. Antony K.M. Ganu R. Petrosino J. Versalovic J. The placenta harbors a unique microbiome. Sci. Transl. Med. 2014; 6: 237ra65 Adamski F.M. King A.T. Demmer J. Expression of the Fc receptor in the mammary gland during lactation in the marsupial Trichosurus vulpecula (brushtail possum). Mol. Immunol. 2000; 37: 435-444 Ahmed T. Fuchs G.J. Gastrointestinal allergy to food: a review. J. Diarrhoeal Dis. Res. 1997; 15: 211-223 Andreas N.J. Kampmann B. Mehring Le-Doare K.
COVID-19-neutralizing antibodies predict disease severity and survival
Highlights • Severe COVID-19 associates with higher antibody production and neutralization titers • Neutralization potency of anti-RBD antibodies predicts disease severity and survival • Immunomodulatory COVID-19-directed therapies modulate antibody responses • COVID-19 sera neutralize D614 and G614 variants, but not pre-emergent WIV1-CoV Summary Coronavirus disease 2019 (COVID-19) exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between...
Passive Transfer of Vaccine-Elicited Antibodies Protects against SIV in Rhesus Macaques
Highlights • We defined a putative protective SIV signature based on multiple antibody functions • Passive transfer of IgG from vaccinated macaques partially protected against SIV • These data demonstrate protective efficacy of vaccine-elicited antibodies in macaques Summary Several HIV-1 and SIV vaccine candidates have shown partial protection against viral challenges in rhesus macaques.
Passive Transfer of Vaccine-Elicited Antibodies Protects against SIV in Rhesus Macaques
Highlights • We defined a putative protective SIV signature based on multiple antibody functions • Passive transfer of IgG from vaccinated macaques partially protected against SIV • These data demonstrate protective efficacy of vaccine-elicited antibodies in macaques Summary Several HIV-1 and SIV vaccine candidates have shown partial protection against viral challenges in rhesus macaques.
The Power of Antibody-Based Surveillance
6 References Related Articles Article Antibodies are immune proteins that mark the evolution of the host immune response to infection. Antibodies can be measured in a sensitive and specific manner, providing an archive that reflects recent or previous infection. If maintained at sufficiently high levels, antibodies can rapidly block infection on reexposure, conferring long-lived protection.
Dissecting antibody-mediated protection against SARS-CoV-2
Understanding the properties and mechanisms by which antibodies provide protection is essential to defining immunity. Although neutralizing antibodies have been proposed as a potential key mechanism of protection against many viral pathogens, antibodies mediate additional immune functions that may have both protective and pathological consequences.
Saving the most vulnerable from COVID-19
Home Life Health Article Much emphasis has been placed on building lab capacity for polymerase chain reaction tests, the gold standard for detecting the COVID-19 virus A woman wearing a mask shops at Portobello Road Market, following the outbreak of the coronavirus disease (COVID-19), London, Britain, June 1, 2020.
Saving the most vulnerable from Covid-19 pandemic
By Simon Johnson, Galit Alter, Tess Cameron, and Michael Mina Cambridge In Massachusetts, which has a population of close to 7mn, over 6,000 people have died from Covid-19 since the beginning of March. But one relatively small group – including about 38,000 people, or 0.5% of the state’s population – accounts for 60% of these deaths.
Opinion | Beware of studies claiming covid-19 death rates are smaller than expected
Please Note The Washington Post is providing this important information about the coronavirus for free. For more free coverage of the coronavirus pandemic, where all stories are free to read. George Q. Daley is the dean of Harvard Medical School. Stephen Elledge is a professor and researcher at Brigham and Women’s Hospital. Galit Alter is a professor and researcher at the Ragon Institute and Massachusetts General Hospital. Michael Springer is an associate professor at Harvard Medical School.
Neonate-omics: Charting the Unknown Immune Response in Early Life
The study of neonatal immunology has been hampered by lack of access to infant samples. Novel sample sparing methods and systems-wide approaches have uniquely expanded this field, demonstrating that newborn immunity varies widely but converges over the first 3 months of life. During this important time window, environmental and genetic factors impact the infant immune system and can influence lifelong immunity.
Immune Correlate-Guided HIV Vaccine Design
Although vaccines have been successfully developed against several pathogens, designing an effective vaccine to protect against human immunodeficiency virus (HIV) has remained an intractable challenge. To address this, the research community has looked to human and non-human primate studies to understand the correlates of protective immunity, based on which a targeted vaccine strategy may be designed. Two distinct approaches, focused on different immune correlates of protection, have emerged.
Opportunities to exploit antibody glycosylation in vaccination
G Alter is NIH funded (grant number R01 102660-01). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
The HIV-1 Glycan Shield: Strategically Placed Kinks in the Armor Improve Antigen Design
The HIV-1 envelope glycoprotein is decorated with a dense array of glycans that masks nearly the entire surface of the infectious envelope, posing a significant barrier to antibodies that aim to target sites of neutralization vulnerability.
Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects
Diverse Ab effector functions mediated by the Fc domain have been commonly associated with reduced risk of infection in a growing number of nonhuman primate and human clinical studies.
Broadly Neutralizing Antibodies: Magic Bullets against HIV?
Broadly neutralizing antibodies (bNAbs) offer new avenues for HIV prevention and cure strategies. Three recent papers, published in Science and Nature, highlight the broad applicability of bNAbs in HIV cure and prevention and in boosting immunity against HIV. To access this article, please choose from the options below Purchase access to this article Claim Access If you are a current subscriber with Society Membership or an Account Number, claim your access now.
Defining the phenotype and transcriptome of IgG3+ B cells
Recent studies suggest that highly polyfunctional non-neutralizing HIV-specific IgG3 antibodies are associated with protection from HIV infection in the RV144 HIV vaccine trial. While it is well established that IgG3 Abs can drive a wide range of Fc-mediated innate effector functions, it remains unclear whether intrinsic factors are important for selection and maintenance of IgG3-secreting B cells and what extrinsic signals preferentially induce IgG3 class-switch.
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