A New Vaccine to Battle Covid-19 Haynes, Barton F
The New England journal of medicine,
02/2021, Volume:
384, Issue:
5
Journal Article
Peer reviewed
Open access
The United States and many parts of the world have now lost control of the Covid-19 pandemic owing to the respiratory spread of SARS-CoV-2 and to inconsistent adherence to effective public health ...measures, including wearing masks and maintaining social distancing. Persons infected with SARS-CoV-2 are frequently asymptomatic, yet they have high respiratory viral loads, and they are major purveyors of viral spread. These factors have led to the current explosion of Covid-19 hospitalizations and deaths, with Covid-19 now a major cause of death in the United States. Our only hope is safe and effective vaccines that can be widely deployed . . .
Summary
The development of an effective vaccine has been hindered by the enormous diversity of human immunodeficiency virus‐1 (HIV‐1) and its ability to escape a myriad of host immune responses. In ...addition, conserved vulnerable regions on the HIV‐1 envelope glycoprotein are often poorly immunogenic and elicit broadly neutralizing antibody responses (BNAbs) in a minority of HIV‐1‐infected individuals and only after several years of infection. All of the known BNAbs demonstrate high levels of somatic mutations and often display other unusual traits, such as a long heavy chain complementarity determining region 3 (CDRH3) and autoreactivity that can be limited by host tolerance controls. Nonetheless, the demonstration that HIV‐1‐infected individuals can make potent BNAbs is encouraging, and recent progress in isolating such antibodies and mapping their immune pathways of development is providing new strategies for vaccination.
Highlights • New progress has been made in understanding effective protective mechanisms of anti-HIV CD8 cytolytic T lymphocytes. • New progress has been made in understanding the mechanisms of ...induction of broadly reactive neutralizing antibodies. • New progress has been made in elucidation of the structure of the HIV envelope trimer. • New strategies have been developed for induction of protective T and B cell responses to HIV infection.
This Pillars of Immunology article is a commentary on “HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease,” a pivotal article written by G. ...Pantaleo, C. Graziosi, J. F. Demarest, L. Butini, M. Montroni, C. H. Fox, J. M. Orenstein, D. P. Kotler, and A. S. Fauci, and published in Nature, in 1993. https://www.nature.com/articles/362355a0. The Journal of Immunology, 2023, 210: 1181–1182
Prophylactic and therapeutic drugs are urgently needed to combat coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over the past year, ...SARS-CoV-2 neutralizing antibodies have been developed for preventive or therapeutic uses. While neutralizing antibodies target the spike protein, their neutralization potency and breadth vary according to recognition epitopes. Several potent SARS-CoV-2 antibodies have shown degrees of success in preclinical or clinical trials, and the US Food and Drug Administration has issued emergency use authorization for two neutralizing antibody cocktails.Nevertheless, antibody therapy for SARS-CoV-2 still faces potential challenges, including emerging viral variants of concern that have antibody-escape mutations and the potential for antibody-mediated enhancement of infection or inflammation. This review summarizes representative SARS-CoV-2 neutralizing antibodies that have been reported and discusses prospects and challenges for the development of the next generation of COVID-19 preventive or therapeutic antibodies.
Summary
Induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccine development. BNAbs are made during HIV infection by a subset of individuals but currently cannot be induced ...in the setting of vaccination. Considerable progress has been made recently in understanding host immunologic controls of bNAb induction and maturation in the setting of HIV infection, and point to key roles for both central and peripheral immunologic tolerance mechanisms in limiting bnAb development. Immune tolerance checkpoint inhibition has been transformative in promotion of anti‐tumor CD8 T‐cell responses in the treatment of certain malignancies. Here, we review the evidence for host controls of bNAb responses, and discuss strategies for the transient modulation of immune responses with vaccines toward the goal of enhancing germinal center B‐cell responses to favor bNAb B‐cell lineages and to foster their maturation to full neutralization potency.
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