Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC) DOI Creative Commons
Sindhu Mohandas, Prasanna Jagannathan, Timothy J. Henrich

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 26, 2023

With a global tally of more than 500 million cases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date, there are growing concerns about the post-acute sequelae SARS-CoV-2 infection (PASC), also known as long COVID. Recent studies suggest that exaggerated immune responses key determinants severity and outcomes initial well subsequent PASC. The complexity innate adaptive in period requires in-depth mechanistic analyses identify specific molecular signals cell populations which promote PASC pathogenesis. In this review, we examine current literature on mechanisms dysregulation COVID-19 limited emerging data immunopathology While phases may share some parallel immunopathology, it is likely quite distinct heterogeneous, thus requiring large-scale longitudinal patients with without after an infection. By outlining knowledge gaps PASC, hope provide avenues for novel research directions will ultimately lead precision therapies restore healthy function patients.

Language: Английский

The T cell immune response against SARS-CoV-2 DOI Open Access
Paul Moss

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(2), P. 186 - 193

Published: Feb. 1, 2022

Language: Английский

Citations

1110
mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern DOI Creative Commons
Rishi R. Goel, Mark M. Painter, Sokratis A. Apostolidis

et al.

Science, Journal Year: 2021, Volume and Issue: 374(6572)

Published: Oct. 15, 2021

Immune memory after vaccination Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven highly effective at preventing COVID-19. However, the evolution of viral variants, and waning antibody levels over time, raise questions regarding longevity vaccine-induced immune protection. Goel et al . examined B T lymphocyte responses in individuals who received SARS-CoV-2 messenger RNA vaccines. They performed a 6-month longitudinal study never had infection compared with people recovered from SARS-CoV-2. Humoral cellular was observed vaccinated individuals, as were functional Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) variants. Analysis cell activity suggested that robust may prevent hospitalization by limiting development disease. —PNK

Language: Английский

Citations

807
T cell responses to SARS-CoV-2 spike cross-recognize Omicron DOI Creative Commons
Roanne Keeton, Marius B. Tincho, Amkele Ngomti

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7901), P. 488 - 492

Published: Jan. 31, 2022

Abstract The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations 1,2 that contribute to viral escape from antibody neutralization 3–6 and reduce vaccine protection infection 7,8 . extent which other components of the adaptive response such as T cells may still target severe outcomes is unknown. Here we assessed ability react in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, unvaccinated convalescent COVID-19 patients ( n = 70). Between 70% 80% CD4 + CD8 cell was maintained across study groups. Moreover, magnitude cross-reactive similar for Beta (B.1.351) Delta (B.1.617.2) variants, despite harbouring considerably more mutations. In hospitalized infections 19), there comparable responses ancestral spike, nucleocapsid membrane proteins those previous waves dominated by ancestral, variants 49). Thus, extensive reduced susceptibility neutralizing antibodies Omicron, majority induced vaccination cross-recognize variant. It remains be determined whether well-preserved immunity contributes linked early clinical observations South Africa elsewhere 9–12

Language: Английский

Citations

548
Homologous and Heterologous Covid-19 Booster Vaccinations DOI Open Access
Robert L. Atmar, Kirsten E. Lyke, Meagan E. Deming

et al.

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 386(11), P. 1046 - 1057

Published: Jan. 26, 2022

Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in United States are highly effective, breakthrough infections occurring. Data needed on serial of homologous boosters (same as primary vaccine) and heterologous (different from fully vaccinated recipients.In this phase 1-2, open-label clinical trial conducted at 10 sites States, adults who had completed a Covid-19 vaccine regimen least 12 weeks earlier no reported history severe acute respiratory syndrome 2 (SARS-CoV-2) infection booster injection with one vaccines: mRNA-1273 (Moderna) dose 100 μg, Ad26.COV2.S (Johnson & Johnson-Janssen) 5×1010 virus particles, or BNT162b2 (Pfizer-BioNTech) 30 μg. The end points were safety, reactogenicity, humoral immunogenicity days 15 29.Of 458 participants enrolled trial, 154 mRNA-1273, 150 Ad26.COV2.S, 153 vaccines; 1 participant did not receive assigned vaccine. Reactogenicity was similar to for series. More than half recipients having injection-site pain, malaise, headache, myalgia. For all combinations, antibody neutralizing titers SARS-CoV-2 D614G pseudovirus increased by factor 4 73, binding 5 55. Homologous 20, whereas 6 73. Spike-specific T-cell responses but Ad26.COV2.S-boosted subgroup. CD8+ levels more durable Ad26.COV2.S-primed recipients, boosting substantially spike-specific T cells mRNA recipients.Homologous an acceptable safety profile immunogenic earlier. (Funded National Institute Allergy Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).

Language: Английский

Citations

544
Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by cross-reactive T cells DOI Creative Commons
José Mateus, Jennifer M. Dan, Zeli Zhang

et al.

Science, Journal Year: 2021, Volume and Issue: 374(6566)

Published: Sept. 14, 2021

A smaller-dose jab does the job Low-dose messenger RNA (mRNA) vaccines potentially allow health providers to administer more doses from a limited vaccine supply and can be less reactogenic. Whether low-dose COVID-19 mRNA generate immune responses comparable currently approved remains an open question, however. Mateus et al . report results of clinical trial comparing patients who received 25-μg mRNA-1273 (Moderna) 100-μg vaccinees severe acute respiratory syndrome coronavirus 2–infected individuals. The Moderna generated long-lived T cell immunity that was equivalent between younger older could enhanced by presence cross-reactive cells. Moreover, antibody induced were natural infection about half as strong those seen with high-dose vaccination. —STS

Language: Английский

Citations

299
SARS-CoV-2 Variants, Vaccines, and Host Immunity DOI Creative Commons
Priyal Mistry, Fatima Barmania, Juanita Mellet

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 3, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new beta that emerged at the end of 2019 in Hubei province China. SARS-CoV-2 causes disease (COVID-19) and was declared pandemic by World Health Organization (WHO) on 11 March 2020. Herd or community immunity has been proposed as strategy to protect vulnerable, can be established through from past infection vaccination. Whether results development reservoir resilient memory cells under investigation. Vaccines have developed an unprecedented rate 7 408 870 760 vaccine doses administered worldwide. Recently variants are more transmissible with reduced sensitivity immune mechanisms. This due presence amino acid substitutions spike protein, which confer selective advantage. The emergence therefore poses risk for effectiveness long-term immunity, it crucial determine vaccines against currently circulating variants. Here we review both SARS-CoV-2-induced host activation vaccine-induced responses, highlighting responses key indicators immunity. We further discuss how emerge concern (VOC), particular focus implications effectiveness. Finally, describe antibody treatments future approaches will important navigate COVID-19 pandemic.

Language: Английский

Citations

282
Correlates of protection against SARS‐CoV‐2 infection and COVID‐19 disease DOI
David Goldblatt, Galit Alter, Shane Crotty

et al.

Immunological Reviews, Journal Year: 2022, Volume and Issue: 310(1), P. 6 - 26

Published: June 5, 2022

Antibodies against epitopes in S1 give the most accurate CoP infection by SARS-CoV-2 coronavirus. Measurement of those antibodies neutralization or binding assays both have predictive value, with antibody titers giving highest statistical correlation. However, protective functions are multiple. multiple other than influence efficacy. The role cellular responses can be discerned respect to CD4

Language: Английский

Citations

244
Immunological memory to SARS‐CoV ‐2 infection and COVID ‐19 vaccines DOI Creative Commons
Alessandro Sette, Shane Crotty

Immunological Reviews, Journal Year: 2022, Volume and Issue: 310(1), P. 27 - 46

Published: June 22, 2022

Immunological memory is the basis of protective immunity provided by vaccines and previous infections. can develop from multiple branches adaptive immune system, including CD4 T cells, CD8 B long-lasting antibody responses. Extraordinary progress has been made in understanding to SARS-CoV-2 infection COVID-19 vaccines, addressing development; quantitative qualitative features different cellular anatomical compartments; durability each component antibodies. Given sophistication measurements; size human studies; use longitudinal samples cross-sectional head-to-head comparisons between or for 1 year already supersedes that any other acute infectious disease. This knowledge may help inform public policies regarding as well scientific development future against diseases.

Language: Английский

Citations

218
SARS-CoV-2 infection generates tissue-localized immunological memory in humans DOI Creative Commons

Maya M.L. Poon,

Ksenia Rybkina,

Yu Kato

et al.

Science Immunology, Journal Year: 2021, Volume and Issue: 6(65)

Published: Oct. 17, 2021

Adaptive immune responses to SARS-CoV-2 infection have been extensively characterized in blood; however, most functions of protective immunity must be accomplished tissues. Here, we report from examination seropositive organ donors (ages 10 74) that CD4+ T, CD8+ and B cell memory generated response is present the bone marrow, spleen, lung, multiple lymph nodes (LNs) for up 6 months after infection. Lungs lung-associated LNs were prevalent sites SARS-CoV-2–specific T cells with significant correlations between circulating tissue-resident all sites. We further identified germinal centers follicular helper also abundant lungs. Together, results indicate local tissue coordination cellular humoral against site-specific protection future infectious challenges.

Language: Английский

Citations

200
COVID-19 vaccination: The road ahead DOI
Daniel M. Altmann, Rosemary J. Boyton

Science, Journal Year: 2022, Volume and Issue: 375(6585), P. 1127 - 1132

Published: March 10, 2022

A diverse array of successful, first-generation SARS-CoV-2 vaccines have played a huge role in efforts to bring the COVID-19 pandemic under control, even though inequitable distribution still leaves many vulnerable. Additional challenges loom for next phase. These include optimizing immunological rationale boosting-how often and with what-and best approaches building future-proofed, durable immune repertoire protect against oncoming viral variants, including children. The landscape vaccine producers technologies is likely become more heterogeneous. There need now appraisal future approaches: While some favor frequent boosting first-generation, ancestral spike vaccines, others propose readjustment using current variant sequences, polyvalent or pan-coronavirus strategies.

Language: Английский

Citations

184