Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Янв. 22, 2024

Background The coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although current rate Severe acute respiratory syndrome 2 (SARS-CoV-2) infections decreased significantly, long-term outlook COVID-19 remains serious cause morbidity and mortality worldwide, with still substantially surpassing even that recorded for influenza viruses. continued emergence SARS-CoV-2 variants concern (VOCs), including multiple heavily mutated Omicron sub-variants, prolonged underscores urgent need next-generation vaccine will protect from VOCs. Methods We designed multi-epitope-based incorporated B, CD4 + , CD8 T- cell epitopes conserved among all known VOCs selectively recognized by T-cells asymptomatic patients irrespective VOC infection. safety, immunogenicity, cross-protective immunity this pan-variant were studied against six using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model. Results (i) is safe (ii) induces high frequencies lung-resident functional T EM RM cells (iii) provides robust protection virus replication. COVID-19-related lung pathology death caused VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2), (B.1.1.529). Conclusion A multi-epitope bearing human B- structural non-structural antigens induced facilitated clearance, reduced morbidity, pathology,

Язык: Английский

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Breakthrough infections after COVID-19 vaccination: Insights, perspectives and challenges

Metabolism Open, Год журнала: 2022, Номер 14, С. 100180 - 100180

Опубликована: Март 17, 2022

Vaccination programs against SARS-CoV-2 constitute the mainstay of public health interventions global COVID-19 pandemic. Currently available vaccines have shown 90% or better rates protection severe disease and mortality. Barely a year after became available, Omicron variant its unprecedented speed transmission has posed new challenge. Overall, presents increased immune escape, transmissibility, decreased pathogenicity. Vaccines do not offer full acquisition, since "breakthrough" infections may occur in fully vaccinated individuals, who turn spread virus to others. Breakthrough be causally related viral profile (viral load, incubation period, pathogenicity, evasion), immunity characteristics (mucosal versus systemic immunity, duration etc.), host determinants (age, comorbidities, status, immunosuppressive drugs) vaccination properties (platform, antigen dose, dose number, interval, route administration). Determining rate breakthrough challenging necessitates conduction population-based studies regarding vaccine effectiveness as well neutralizing antibody testing, surrogate protection. In this review, we analyze causes infections, their clinical consequences (severity infection transmission), methods determining incidence challenges perspectives. Long COVID multi-inflammatory syndrome adolescents significantly reduced infections. The need for universal pancoranavirus that would aim at protecting plethora variants emerging is discussed. Finally, novel strategies, such nasal vaccines, confer robust mucosal protection, reducing efficiently transmission.

Язык: Английский

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Sensitivity to Vaccines, Therapeutic Antibodies, and Viral Entry Inhibitors and Advances To Counter the SARS-CoV-2 Omicron Variant

Clinical Microbiology Reviews, Год журнала: 2022, Номер 35(3)

Опубликована: Июнь 6, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and mutating into newer variants over time, which gain higher transmissibility, disease severity, spread in communities at a faster rate, resulting multiple waves of surge Coronavirus Disease 2019 (COVID-19) cases. A highly mutated transmissible SARS-CoV-2 Omicron variant has recently emerged, driving the extremely high peak infections almost all continents an unprecedented speed scale. The evades protection rendered by vaccine-induced antibodies natural infection, as well overpowers antibody-based immunotherapies, raising concerns current effectiveness available vaccines monoclonal therapies. This review outlines most recent advancements studying virology biology variant, highlighting its increased resistance to therapeutics immune escape against vaccines. However, is sensitive viral fusion inhibitors targeting HR1 motif spike protein, enzyme inhibitors, involving endosomal pathway, ACE2-based entry inhibitors. variant-associated infectivity mechanisms are essentially distinct from previous characterized variants. Innate sensing evasion T cell immunity virus provide new perspectives vaccine drug development. These findings important for understanding advances developing vaccines, therapies, more effective strategies mitigate transmission or next concern.

Язык: Английский

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SARS-CoV-2 hybrid immunity: silver bullet or silver lining?

Nature reviews. Immunology, Год журнала: 2022, Номер 22(10), С. 591 - 592

Опубликована: Авг. 9, 2022

Язык: Английский

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Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history

Cell Host & Microbe, Год журнала: 2022, Номер 30(12), С. 1745 - 1758.e7

Опубликована: Окт. 21, 2022

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, both. We measured their neutralization titers against 15 natural and 7 engineered spike mutations analyzed antigenic diversity. Antigenic maps primary sera showed that Omicron sublineages BA.2, BA.4/BA.5, BA.2.12.1 are distinct BA.1 more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased than BA.4/BA.5 BA.2.12.1. post-vaccination elicited higher all three alone, although less BA.4/BA.5. Those after two had titer magnitude recognition. Accounting for differences among when interpreting can aid the understanding complex patterns in humoral immunity informs selection future strains.

Язык: Английский

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