Adaptive immune responses to SARS-CoV-2

Forthal, Donald N.

doi:10.1016/j.addr.2021.02.009

Cited by 7 publications

(10 citation statements)

References 115 publications

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“…et al ( 245 ) defined most SARS-CoV-2 CD4+ T cells as displaying a central memory profile. Furthermore, Gurevich M. et al ( 221 ) reported the presence of IL-2-secreting and IFN-γ+IL-2-secreting SARS-CoV-2-specific central memory T cells that might be long-lasting memory phenotypes in accordance with previous studies ( 246 ). There are two different subsets of CCR7+ stem cell-like progenitors: CCR7+PD-1−TIGIT− cells are observed to display stem cell-like features, whereas CCR7+PD-1+TIGIT+ cells seem to exhibit exhausted traits ( 192 , 247 ).…”

Section: Immune Memorysupporting

confidence: 82%

The Robustness of Cellular Immunity Determines the Fate of SARS-CoV-2 Infection

2022

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Two years after the appearance of the SARS-CoV-2 virus, the causal agent of the current global pandemic, it is time to analyze the evolution of the immune protection that infection and vaccination provide. Cellular immunity plays an important role in limiting disease severity and the resolution of infection. The early appearance, breadth and magnitude of SARS-CoV-2 specific T cell response has been correlated with disease severity and it has been thought that T cell responses may be sufficient to clear infection with minimal disease in COVID-19 patients with X-linked or autosomal recessive agammaglobulinemia. However, our knowledge of the phenotypic and functional diversity of CD8+ cytotoxic lymphocytes, CD4+ T helper cells, mucosal-associated invariant T (MAIT) cells and CD4+ T follicular helper (Tfh), which play a critical role in infection control as well as long-term protection, is still evolving. It has been described how CD8+ cytotoxic lymphocytes interrupt viral replication by secreting antiviral cytokines (IFN-γ and TNF-α) and directly killing infected cells, negatively correlating with stages of disease progression. In addition, CD4+ T helper cells have been reported to be key pieces, leading, coordinating and ultimately regulating antiviral immunity. For instance, in some more severe COVID-19 cases a dysregulated CD4+ T cell signature may contribute to the greater production of pro-inflammatory cytokines responsible for pathogenic inflammation. Here we discuss how cellular immunity is the axis around which the rest of the immune system components revolve, since it orchestrates and leads antiviral response by regulating the inflammatory cascade and, as a consequence, the innate immune system, as well as promoting a correct humoral response through CD4+ Tfh cells. This review also analyses the critical role of cellular immunity in modulating the development of high-affinity neutralizing antibodies and germinal center B cell differentiation in memory and long-lived antibody secreting cells. Finally, since there is currently a high percentage of vaccinated population and, in some cases, vaccine booster doses are even being administered in certain countries, we have also summarized newer approaches to long-lasting protective immunity and the cross-protection of cellular immune response against SARS-CoV-2.

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Section: Immune Memorysupporting

confidence: 82%

The Robustness of Cellular Immunity Determines the Fate of SARS-CoV-2 Infection

2022

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“…The HCPS case fatality rates can reach 20–40% [ 28 , 29 ]. Several Orthohantavirus species have been recognized as aetiological agents of HCPS, including the Sin Nombre orthohantavirus (SNV) and Andes orthohantavirus (ANDV) as the most relevant species in North America and South America, respectively [ 30 , 31 ]. Clinically, HCPS is characterized by an initial short prodromal period, with flu-like symptoms such as fever, headache, cough, myalgia, and gastrointestinal discomfort [ 29 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

BCG-Based Vaccines Elicit Antigen-Specific Adaptive and Trained Immunity against SARS-CoV-2 and Andes orthohantavirus

et al. 2022

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Background:Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a live attenuated vaccine mainly administered to newborns and used for over 100 years to prevent the disease caused by Mycobacterium tuberculosis (M. tb). This vaccine can induce immune response polarization towards a Th1 profile, which is desired for counteracting M. tb, other mycobacteria, and unrelated intracellular pathogens. The vaccine BCG has been used as a vector to express recombinant proteins and has been shown to protect against several diseases, particularly respiratory viruses. Methods: BCG was used to develop recombinant vaccines expressing either the Nucleoprotein from SARS-CoV-2 or Andes orthohantavirus. Mice were immunized with these vaccines with the aim of evaluating the safety and immunogenicity parameters. Results: Immunization with two doses of 1 × 108 CFU or one dose of 1 × 105 CFU of these BCGs was safe in mice. A statistically significant cellular immune response was induced by both formulations, characterized as the activation of CD4+ and CD8+ T cells. Stimulation with unrelated antigens resulted in increased expression of activation markers by T cells and secretion of IL-2 and IFN-γ, while increased secretion of IL-6 was found for both recombinant vaccines; all of these parameters related to a trained immunity profile. The humoral immune response elicited by both vaccines was modest, but further exposure to antigens could increase this response. Conclusions: The BCG vaccine is a promising platform for developing vaccines against different pathogens, inducing a marked antigen-specific immune response.

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“…The findings of IFNg-secreting effector MTC suggest an immediate, but not sustained protection at pathogen sites of entry, whereas central MTC characterized by IL2 or IFNg+IL2 secretion suggests a sustained long-lasting response by proliferating in the secondary lymphoid organs and producing a supply of new effectors (Forthal 2021).…”

Section: Discussionmentioning

confidence: 89%

“…Prevention from re-infection involves cellular memory components programmed to rapidly response to antigen encounter generating memory B and T cells (Cromer et al 2021 ;Forthal 2021 ;Mazzoni et al 2021 ;Turner et al 2021 ;Ueffing et al 2020). Our study demonstrates the simultaneous presence of robust SARS-COV-2 anti-spike antibodies, and durable memory B and T cell responses specific for SARS-COV-2 peptides in subjects recovered from COVID-19 up to 7-months postinfection.…”

Section: Discussionmentioning

confidence: 99%

“…This draws attention to longstanding immunity against SARS-COV-2 involving memory B and memory T cells (MBC and MTC, respectively). The presence of specific anti-SARS-COV-2 MBC and MTC was demonstrated in convalescent patients (Forthal 2021 ;Hartley et al 2020 ;Peng et al 2006 ;Peng et al 2020 ;Rodda et al 2021 ; Schwarzkopf et al 2021 ;Sekine et al 2020 ;Sherina et al 2021 ;Thieme et al 2020).…”

Section: Introductionmentioning

confidence: 99%

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SARS‐CoV‐2 memory B and T cell profiles in mild COVID‐19 convalescent patients

Gurevich

Zilkha‐Falb

Sonis

et al. 2022

International Journal of Infectious Diseases

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Objectives . Antiviral adaptive immunity involves memory B-(MBC) and T-cells (MTC), however their dynamics in SARS-CoV-2 convalescents warrant further investigation. Methods . In the cross-sectional and longitudinal study, we evaluated blood-derived MBC- and MTC-responses in 68 anti-spike IgG-positive mild-COVID-19 convalescents at visit 1 between 1-7 months (median 4.1 months) after disease onset. SARS-CoV-2 anti-spike IgG was performed by ELISA, MBC by SARS-COV-2 specific receptor binding domain (RBD) Elispot and Interferon gamma (IFNg), interleukin 2 (IL2) and IFNg+IL2 secreting MTC by IFNg and IL2 SARS-CoV-2 FluoroSpot. For 24 patients sampled at first visit, the IgG, MBC and MTC analysis were also performed 3 months later at second visit. Results . Seventy two percent were both MBC- and MTC-positive, 18 % - MBC-positive and MTC-negative, and 10% - MTC-positive and MBC-negative. The peak of MBC-response level was detected at 3 months after COVID-19 onset and persisted up to 7 months post infection. A significant MTC-levels were detected one month after onset in response to S1, S2_N and SNMO peptide pools. The frequency and magnitude of MTC response to SNMO was higher than to S1 and S2_N. Longitudinal analysis demonstrated that even when specific humoral immunity declined, the cellular immunity persisted. Conclusion . Our findings demonstrate durability of adaptive cellular immunity at least for 7-months after SARS-CoV-2 infection that suggest long-lasting protection.

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Adaptive immune responses to SARS-CoV-2

Cited by 7 publications

References 115 publications

The Robustness of Cellular Immunity Determines the Fate of SARS-CoV-2 Infection

The Robustness of Cellular Immunity Determines the Fate of SARS-CoV-2 Infection

BCG-Based Vaccines Elicit Antigen-Specific Adaptive and Trained Immunity against SARS-CoV-2 and Andes orthohantavirus

SARS‐CoV‐2 memory B and T cell profiles in mild COVID‐19 convalescent patients

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