T-Helper Cell Subset Response Is a Determining Factor in COVID-19 Progression

Gil‐Etayo, Francisco Javier; Suàrez-Fernández, Patricia; Cabrera-Marante, Óscar; Arroyo, Daniel; Garcinuño, Sara; Naranjo, Laura; Pleguezuelo, Daniel; Allende, Luís M.; Mancebo, Esther; Lalueza, Antonio; Díaz-Simón, Raquel; Paz‐Artal, Estela; Serrano, Antonio

doi:10.3389/fcimb.2021.624483

Cited by 135 publications

(161 citation statements)

References 83 publications

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“…In contrast, another study found a lower distribution of Th1, TH17 compared to a higher percentage of Th2 cells in COVID-19 patients. Interestingly, this study also found an increase in senescent Th2 cells in patients who died from COVID-19 ( 107 ). In a different post-mortem study on severe COVID patients, lymph and spleen analysis revealed a lack of germinal centres, an increase in Th1 cells and a decrease in Th2 cells ( 108 ).…”

Section: Sars-cov-2 and The Immunity Phasesupporting

confidence: 62%

Infection and Immune Memory: Variables in Robust Protection by Vaccines Against SARS-CoV-2

et al. 2021

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SARS-CoV-2 is the cause of a recent pandemic that has led to more than 3 million deaths worldwide. Most individuals are asymptomatic or display mild symptoms, which raises an inherent question as to how does the immune response differs from patients manifesting severe disease? During the initial phase of infection, dysregulated effector immune cells such as neutrophils, macrophages, monocytes, megakaryocytes, basophils, eosinophils, erythroid progenitor cells, and Th17 cells can alter the trajectory of an infected patient to severe disease. On the other hand, properly functioning CD4+, CD8+ cells, NK cells, and DCs reduce the disease severity. Detailed understanding of the immune response of convalescent individuals transitioning from the effector phase to the immunogenic memory phase can provide vital clues to understanding essential variables to assess vaccine-induced protection. Although neutralizing antibodies can wane over time, long-lasting B and T memory cells can persist in recovered individuals. The natural immunological memory captures the diverse repertoire of SARS-CoV-2 epitopes after natural infection whereas, currently approved vaccines are based on a single epitope, spike protein. It is essential to understand the nature of the immune response to natural infection to better identify ‘correlates of protection’ against this disease. This article discusses recent findings regarding immune response against natural infection to SARS-CoV-2 and the nature of immunogenic memory. More precise knowledge of the acute phase of immune response and its transition to immunological memory will contribute to the future design of vaccines and the identification of variables essential to maintain immune protection across diverse populations.

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Section: Sars-cov-2 and The Immunity Phasesupporting

confidence: 62%

Infection and Immune Memory: Variables in Robust Protection by Vaccines Against SARS-CoV-2

et al. 2021

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“…For example, US Food and Drug Administration guidelines for influenza vaccine development rely on hemagglutination-inhibiting (HI) antibody titers, i.e., percentage of subjects achieving an HI antibody titer of at least 1:40 and rates of seroconversion (change in titer from less than 1:10 to at least 1:40 or fourfold rise in HI antibody titer) [ 71 ]. T cells have been demonstrated to play a role in the immune response to SARS-CoV-2 [ 72 , 73 ], but such responses are difficult to measure, which has prevented a full understanding of the role of T cells in an effective vaccine response against SARS-CoV-2. Because these data on cellular responses to vaccination are limited, the extent to which any one individual or group of individuals responds to vaccination is difficult to ascertain.…”

Section: The Immune Systemmentioning

confidence: 99%

Vaccine Considerations for Multiple Sclerosis in the COVID-19 Era

et al. 2021

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People with multiple sclerosis (MS) are at risk for infections that can result in amplification of baseline symptoms and possibly trigger clinical relapses. Vaccination can prevent infection through the activation of humoral and cellular immune responses. This is particularly pertinent in the era of emerging novel vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). MS disease-modifying therapies (DMTs), which affect the immune system, may impact immune responses to COVID-19 vaccines in people with MS. The objective of this article is to provide information on immune system responses to vaccinations and review previous studies of vaccine responses in people with MS to support the safety and importance of receiving currently available and emerging COVID-19 vaccines. Immunological studies have shown that coordinated interactions between T and B lymphocytes of the adaptive immune system are key to successful generation of immunological memory and production of neutralizing antibodies following recognition of vaccine antigens by innate immune cells. CD4 + T cells are essential to facilitate CD8 + T cell and B cell activation, while B cells drive and sustain T cell memory. Data suggest that some classes of DMT, including type 1 interferons and glatiramer acetate, may not significantly impair the response to vaccination. DMTs—such as sphingosine-1-phosphate receptor modulators, which sequester lymphocytes from circulation; alemtuzumab; and anti-CD20 therapies, which rely on depleting populations of immune cells—have been shown to attenuate responses to conventional vaccines. Currently, three COVID-19 vaccines have been granted emergency use authorization in the USA on the basis of promising interim findings of ongoing trials. Because analyses of these vaccines in people with MS are not available, decisions regarding COVID-19 vaccination and DMT choice should be informed by data and expert consensus, and personalized with considerations for disease burden, risk of infection, and other factors.

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“…Additionally, Type 1 and Type 2 immunity are not strictly synonymous with cell-mediated and humoral immunity, respectively, with Th1 polarization capable of inducing moderate antibody production [ 15 ]. Because of these considerations, most groups developing vaccines for SARS-CoV-2 have focused on promoting Th1 response due to safety concerns and demonstrated efficacy of Th1 response [ 16 ]. To this end, we deduced that vaccines targeting humoral (B cells) and cytotoxic arms (CD8 + T cells) with concurrent helper signalling (CD4 + T cells), delivered with adjuvants promoting Th1 polarization, may provide optimal immunity against SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

Landscape and selection of vaccine epitopes in SARS-CoV-2

et al. 2021

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Background Early in the pandemic, we designed a SARS-CoV-2 peptide vaccine containing epitope regions optimized for concurrent B cell, CD4+ T cell, and CD8+ T cell stimulation. The rationale for this design was to drive both humoral and cellular immunity with high specificity while avoiding undesired effects such as antibody-dependent enhancement (ADE). Methods We explored the set of computationally predicted SARS-CoV-2 HLA-I and HLA-II ligands, examining protein source, concurrent human/murine coverage, and population coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, sequence conservation, source protein abundance, and coverage of high frequency HLA alleles. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering for surface accessibility, sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites. Results From 58 initial candidates, three B cell epitope regions were identified. From 3730 (MHC-I) and 5045 (MHC-II) candidate ligands, 292 CD8+ and 284 CD4+ T cell epitopes were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we proposed a set of 22 SARS-CoV-2 vaccine peptides for use in subsequent murine studies. We curated a dataset of ~ 1000 observed T cell epitopes from convalescent COVID-19 patients across eight studies, showing 8/15 recurrent epitope regions to overlap with at least one of our candidate peptides. Of the 22 candidate vaccine peptides, 16 (n = 10 T cell epitope optimized; n = 6 B cell epitope optimized) were manually selected to decrease their degree of sequence overlap and then synthesized. The immunogenicity of the synthesized vaccine peptides was validated using ELISpot and ELISA following murine vaccination. Strong T cell responses were observed in 7/10 T cell epitope optimized peptides following vaccination. Humoral responses were deficient, likely due to the unrestricted conformational space inhabited by linear vaccine peptides. Conclusions Overall, we find our selection process and vaccine formulation to be appropriate for identifying T cell epitopes and eliciting T cell responses against those epitopes. Further studies are needed to optimize prediction and induction of B cell responses, as well as study the protective capacity of predicted T and B cell epitopes.

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T-Helper Cell Subset Response Is a Determining Factor in COVID-19 Progression

Cited by 135 publications

References 83 publications

Infection and Immune Memory: Variables in Robust Protection by Vaccines Against SARS-CoV-2

Infection and Immune Memory: Variables in Robust Protection by Vaccines Against SARS-CoV-2

Vaccine Considerations for Multiple Sclerosis in the COVID-19 Era

Landscape and selection of vaccine epitopes in SARS-CoV-2

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