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  1. Article ; Online: Impact of Previous Common Human Coronavirus Exposure on SARS-CoV-2-Specific T-Cell and Memory B-Cell Response after mRNA-Based Vaccination.

    Casado, José L / Vizcarra, Pilar / Martín-Hondarza, Adrián / Blasco, Magdalena / Grandal-Platero, Marta / Haemmerle, Johannes / Fernández-Escribano, Marina / Vallejo, Alejandro

    Viruses

    2023  Volume 15, Issue 3

    Abstract: Objective: T-cell responses against SARS-CoV-2 are observed in unexposed individuals, attributed to previous common human coronavirus (HCoV) infections. We evaluated the evolution of this T-cell cross-reactive response and the specific memory B-cells ( ... ...

    Abstract Objective: T-cell responses against SARS-CoV-2 are observed in unexposed individuals, attributed to previous common human coronavirus (HCoV) infections. We evaluated the evolution of this T-cell cross-reactive response and the specific memory B-cells (MBCs) after the SARS-CoV-2 mRNA-based vaccination and its impact on incident SARS-CoV-2 infections.
    Methods: This was a longitudinal study of 149 healthcare workers (HCWs) that included 85 unexposed individuals that were subdivided according to previous T-cell cross-reactivity, who were compared to 64 convalescent HCWs. Changes in specific T-cell response and memory B-cell (MBC) levels were compared at baseline and after two doses of the SARS-CoV-2 mRNA-based vaccine.
    Results: A cross-reactive T-cell response was found in 59% of unexposed individuals before vaccination. Antibodies against HKU1 positively correlated with OC43 and 229E antibodies. Spike-specific MBCs was scarce in unexposed HCWs regardless of the presence of baseline T-cell cross-reactivity. After vaccination, 92% and 96% of unexposed HCWs with cross-reactive T-cells had CD4+ and CD8+ T-cell responses to the spike protein, respectively. Similar results to that were found in convalescents (83% and 92%, respectively). Contrarily, higher than that which was observed in unexposed individuals without T-cell cross-reactivity showed lower CD4+ and CD8+ T-cell responses (73% in both cases,
    Conclusion: While pre-existing T-cell cross-reactivity enhances the T-cell response after vaccination, it does not increase SARS-CoV-2-specific MBC levels in the absence of previous infection. Overall, the level of specific MBCs determines the time to breakthrough infections, regardless of the presence of T-cell cross-reactivity.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; Longitudinal Studies ; COVID-19/prevention & control ; Antibodies ; Breakthrough Infections ; RNA, Messenger ; Vaccination ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus/genetics
    Chemical Substances Antibodies ; RNA, Messenger ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2023-02-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15030627
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  2. Article ; Online: Lower T cell response against SARS-CoV-2 variants of concern after mRNA vaccine and risk of breakthrough infections in people with HIV.

    Casado, José L / Vizcarra, Pilar / Martín-Colmenarejo, Sara / Del Pino, Judith / Gomez-Maldonado, Sandra / Martín-Hondarza, Adrían / Vallejo, Alejandro

    AIDS (London, England)

    2023  Volume 37, Issue 6, Page(s) 877–882

    Abstract: Objectives: We evaluated T-cell immune responses against SARS-CoV-2 variants of concern (VOC) after vaccination in people with HIV (PWH), and their impact on the incidence of disease.: Methods: A prospective cohort study. Peripheral blood mononuclear ...

    Abstract Objectives: We evaluated T-cell immune responses against SARS-CoV-2 variants of concern (VOC) after vaccination in people with HIV (PWH), and their impact on the incidence of disease.
    Methods: A prospective cohort study. Peripheral blood mononuclear cells (PBMCs) were collected a median of 53 days after second dose of mRNA vaccine. Humoral response and T cell responses against the spike (S) glycoprotein of wild-type SARS-CoV-2 (ancestral Wuhan variant) and mutated S-protein regions found in the Delta and Omicron variants were assessed by flow cytometry analysis.
    Results: In 142 PWH without preceding SARS-CoV-2 infection, bivariate correlations showed a close association between T-cell responses to the different variants. However, despite at least 70% of PWH having a cellular immune response to any variant, CD4 + and CD8 + T cell responses against VOC were lower in frequency and magnitude (-3% and -20% for Delta, -33% and -28% for Omicron variant) compared with that observed against the Wuhan strain. A higher magnitude of SARS-CoV-2 spike-specific CD8 + T cell responses against all the variants was observed in those PWH with greater immune reconstitution. Notably, 27 symptomatic breakthrough infections (19%) in the setting of Delta and Omicron transmission were observed during follow-up, associated with a significant lower humoral and T-cell response to ancestral strain and VOC. On the contrary, only one PWH with COVID-19 (4%) required hospitalization.
    Conclusion: A blunted T-cell response against Delta and Omicron variant is observed in PWH who received two doses of mRNA vaccine. This lower immune response is associated with breakthrough SARS-CoV-2 infections.
    MeSH term(s) Humans ; SARS-CoV-2 ; Breakthrough Infections ; Leukocytes, Mononuclear ; Prospective Studies ; COVID-19/prevention & control ; HIV Infections/complications ; Antibodies, Viral ; mRNA Vaccines
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2023-02-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 639076-6
    ISSN 1473-5571 ; 0269-9370 ; 1350-2840
    ISSN (online) 1473-5571
    ISSN 0269-9370 ; 1350-2840
    DOI 10.1097/QAD.0000000000003504
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  3. Article ; Online: IFN-γ

    Vallejo, Alejandro / Vizcarra, Pilar / Quereda, Carmen / Moreno, Ana / Casado, José Luis

    European journal of clinical investigation

    2021  Volume 51, Issue 12, Page(s) e13636

    Abstract: Background: Healthcare workers (HCWs) are at increased risk since they are directly exposed to SARS-CoV-2-infected patients, and nevertheless, some remain without the development of anti-SARS-CoV-2 antibodies or related symptoms, suggesting less ... ...

    Abstract Background: Healthcare workers (HCWs) are at increased risk since they are directly exposed to SARS-CoV-2-infected patients, and nevertheless, some remain without the development of anti-SARS-CoV-2 antibodies or related symptoms, suggesting less susceptibility to the infection.
    Methods: This cross-sectional, case-control study aimed to compare SARS-CoV-2 T-cell response by two different technologies, the analysis of IFN-γ
    Results: A high proportion of uninfected HCWs (53.8%) had pre-existing IFN-γ
    Conclusions: The good concordance between the proportion of individuals with IFN-γ release after SARS-COV-2 stimulation with the proportion of individuals with specific IFN-γ
    MeSH term(s) Adult ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; COVID-19/immunology ; Case-Control Studies ; Coronavirus Nucleocapsid Proteins ; Cross-Sectional Studies ; Female ; Health Personnel ; Humans ; In Vitro Techniques ; Interferon-gamma/immunology ; Interferon-gamma/metabolism ; Interferon-gamma Release Tests ; Male ; Middle Aged ; Nurses ; Phosphoproteins ; Physicians ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus ; T-Lymphocyte Subsets ; T-Lymphocytes/immunology ; Viral Matrix Proteins
    Chemical Substances Coronavirus Nucleocapsid Proteins ; Phosphoproteins ; Spike Glycoprotein, Coronavirus ; Viral Matrix Proteins ; membrane protein, SARS-CoV-2 ; nucleocapsid phosphoprotein, SARS-CoV-2 ; spike protein, SARS-CoV-2 ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2021-06-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 186196-7
    ISSN 1365-2362 ; 0014-2972 ; 0960-135X
    ISSN (online) 1365-2362
    ISSN 0014-2972 ; 0960-135X
    DOI 10.1111/eci.13636
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    Zs.A 677: Show issues Location:
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  4. Article ; Online: Unravelling hip-spine bone mineral density discordance in people living with HIV.

    Vizcarra, Pilar / Rosillo, Marta / Del Rey, José M / Moreno, Ana / Vivancos, María J / Casado, José L

    Journal of bone and mineral metabolism

    2022  Volume 40, Issue 6, Page(s) 990–997

    Abstract: Introduction: In people living with HIV (PLWH), bone mineral density (BMD) discordance between the lumbar spine (LS) and femoral neck (FN) could be frequent given the high frequency of secondary osteoporosis, including HIV-related factors for bone ... ...

    Abstract Introduction: In people living with HIV (PLWH), bone mineral density (BMD) discordance between the lumbar spine (LS) and femoral neck (FN) could be frequent given the high frequency of secondary osteoporosis, including HIV-related factors for bone disease.
    Materials and methods: Retrospective cohort of PLWH with a dual X-ray absorptiometry scan. Hip-spine BMD discordance was defined as different T-score or Z-scores categories at LS and FN.
    Results: Overall, 865 individuals (mean 49.5 years, female 27%) were included. Osteoporosis diagnosis was four-to-seven times lower when both skeletal sites were affected than when considering the lowest T-score at any site (overall, 21% vs 4%). Hip-spine BMD discordance was observed in 381 (44%) individuals, it increased with age (from 43 to 52%, P = 0.032), and it was mainly due to lower LS-BMD. A lower FN-BMD was associated with older age, lower BMI (P < 0.01), and HIV-related factors, such as low CD4 + T-cell counts, duration of HIV infection, and time on antiretroviral therapy (ART). In a multivariate regression analysis, sex male (Odds Ratio, OR 4.901), hyperparathyroidism (OR, 2.364), and time on ART (OR 1.005 per month) were independently associated with discordance. A higher estimated fracture risk by FRAX equation was observed in individuals with BMD discordance due to lower FN-BMD compared to those with lower LS-BMD (+ 36% for major osteoporotic fracture, P = 0.04; + 135% for hip fracture, P < 0.01).
    Conclusion: Hip-spine BMD discordance is highly prevalent in PLWH and it is associated with classical and HIV-related risk factors, modifying the rate of osteoporosis and fracture risk estimation.
    MeSH term(s) Humans ; Male ; Female ; Bone Density ; HIV Infections/complications ; HIV Infections/drug therapy ; Retrospective Studies ; Absorptiometry, Photon ; Osteoporosis/complications ; Osteoporotic Fractures/complications ; Lumbar Vertebrae/diagnostic imaging ; Risk Factors
    Language English
    Publishing date 2022-08-29
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1295123-7
    ISSN 1435-5604 ; 0914-8779
    ISSN (online) 1435-5604
    ISSN 0914-8779
    DOI 10.1007/s00774-022-01365-z
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    Zs.A 4894: Show issues Location:
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  5. Article: Impact of SARS-CoV-2-specific memory B cells on the immune response after mRNA-based Comirnaty vaccine in seronegative health care workers.

    Vallejo, Alejandro / Vizcarra, Pilar / Martín-Hondarza, Adrián / Gómez-Maldonado, Sandra / Haemmerle, Johannes / Velasco, Héctor / Casado, José L

    Frontiers in microbiology

    2022  Volume 13, Page(s) 1002748

    Abstract: Purpose: To analyze the impact of SARS-COV-2-specific memory B cells (MBC) on the immune response after two doses of mRNA-based Comirnaty COVID-19 vaccine in seronegative health care workers. This study is seeking a rationale for boosting vaccines.: ... ...

    Abstract Purpose: To analyze the impact of SARS-COV-2-specific memory B cells (MBC) on the immune response after two doses of mRNA-based Comirnaty COVID-19 vaccine in seronegative health care workers. This study is seeking a rationale for boosting vaccines.
    Methods: Longitudinal study including 31 seronegative health care workers with undetectable specific MBCs (IgG
    Results: The level of specific MBCs, and isotypes, in the IgG
    Conclusion: IgG
    Language English
    Publishing date 2022-09-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2022.1002748
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  6. Article: Cellular Responses to Membrane and Nucleocapsid Viral Proteins Are Also Boosted After SARS-CoV-2 Spike mRNA Vaccination in Individuals With Either Past Infection or Cross-Reactivity.

    Vallejo, Alejandro / Martín-Hondarza, Adrián / Gómez, Sandra / Velasco, Héctor / Vizcarra, Pilar / Haemmerle, Johannes / Casado, José L

    Frontiers in microbiology

    2022  Volume 12, Page(s) 812729

    Abstract: SARS-CoV-2 spike mRNA vaccines have shown remarkable clinical efficacy in the general population, although the nature of T-cell priming is not fully understood. We performed longitudinal spike-, membrane-, and nucleocapsid-specific T-cell analysis in ... ...

    Abstract SARS-CoV-2 spike mRNA vaccines have shown remarkable clinical efficacy in the general population, although the nature of T-cell priming is not fully understood. We performed longitudinal spike-, membrane-, and nucleocapsid-specific T-cell analysis in individuals with past infection and infection-naïve individuals with cross-reactivity. We found an additional enhancement of T-cell response to the structural membrane (M) and nucleocapsid (N) SARS-CoV-2 proteins after mRNA vaccine in these individuals. Thus, despite the spike-specific response, we found that the first dose of the vaccine boosted a significant CD8 cell response to M and N proteins, whereas no cellular response to those proteins was found in infection-naïve individuals without pre-existing cross-reactivity who were tested for eventual asymptomatic infection. These findings highlight the additional benefit of mRNA vaccines as broad boosters of cellular responses to different viral epitopes in these individuals and suggest extended protection to other viral variants.
    Language English
    Publishing date 2022-02-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.812729
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  7. Article ; Online: Low risk of bacterial co-infection, opportunistic diseases, and persistent immunosuppression in people living with HIV and COVID-19.

    Casado, José L / Vizcarra, Pilar / Vivancos, María J / Martinez-Sanz, Javier / Perez-Elías, María J / Moreno, Ana / Vallejo, Alejandro

    Infection

    2022  Volume 50, Issue 4, Page(s) 1013–1017

    Abstract: Purpose: SARS-CoV-2 infection produces lymphopenia and CD4+ T-cell decrease, which could lead to a higher risk of bacterial co-infection or impair immunological evolution in people living with HIV (PLWH).: Methods: We investigated the rate of co- ... ...

    Abstract Purpose: SARS-CoV-2 infection produces lymphopenia and CD4+ T-cell decrease, which could lead to a higher risk of bacterial co-infection or impair immunological evolution in people living with HIV (PLWH).
    Methods: We investigated the rate of co-infection and superinfection, and the evolution of CD4+ count and CD4+/CD8+ ratio, in hospitalized PLWH with COVID-19.
    Results: From March to December 2020, 176 PLWH had symptomatic COVID-19 and 62 required hospitalization (median age, 56 years, 89% males). At admission, 7% and 13% of patients had leukocytosis or increased procalcitonin values and 37 (60%) received empiric antibiotic therapy, but no bacterial co-infection was diagnosed. There were seven cases of superinfection (12%), and one case of P. jiroveci pneumonia during ICU stay. No significant change in CD4+ count or CD4+/CD8+ ratio was observed after discharge.
    Conclusion: Bacterial co-infection is not frequent in PLWH with COVID-19. Immune recovery is observed in most of patients after the disease.
    MeSH term(s) Bacterial Infections/epidemiology ; COVID-19/epidemiology ; COVID-19/immunology ; Coinfection/epidemiology ; Female ; HIV Infections/epidemiology ; HIV Infections/immunology ; Humans ; Immunosuppression Therapy/statistics & numerical data ; Male ; Middle Aged ; Opportunistic Infections/epidemiology ; Risk Assessment
    Language English
    Publishing date 2022-03-31
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 185104-4
    ISSN 1439-0973 ; 0300-8126 ; 0173-2129
    ISSN (online) 1439-0973
    ISSN 0300-8126 ; 0173-2129
    DOI 10.1007/s15010-022-01811-0
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    Zs.A 881: Show issues Location:
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    Zs.MO 528: Show issues

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  8. Article: BNT162b2 mRNA COVID-19 vaccine Reactogenicity: The key role of immunity

    Vizcarra, Pilar / Haemmerle, Johannes / Velasco, Hector / Velasco, Tamara / Fernández-Escribano, Marina / Vallejo, Alejandro / Casado, José L.

    Vaccine. 2021 Dec. 17, v. 39, no. 51

    2021  

    Abstract: We examined the impact of pre-existing SARS-CoV-2-specific cellular immunity on BNT162b2 mRNA COVID-19 vaccine reactogenicity. Of 96 healthcare workers (HCWs), 76% reported any vaccine reaction (first dose: 70%, second dose: 67%), none of which was ... ...

    Abstract We examined the impact of pre-existing SARS-CoV-2-specific cellular immunity on BNT162b2 mRNA COVID-19 vaccine reactogenicity. Of 96 healthcare workers (HCWs), 76% reported any vaccine reaction (first dose: 70%, second dose: 67%), none of which was severe. Following first dose, systemic reactions were significantly more frequent among HCWs with past infection than in infection-naïve individuals, and among HCWs with pre-existing cellular immunity than in those without it. The rate of systemic reactions after second dose was 1.7 and 2.0-times higher than after first dose among infection-naïve HCWs and those without pre-existing cellular immunity, respectively. Levels of SARS-CoV-2-specific T-cells before vaccination were higher in HCWs with systemic reactions after the first dose than in those without them. BNT162b2 vaccine reactogenicity after first dose is attributable to pre-existing cellular immunity elicited by prior COVID-19 or cross-reactivity. Reactogenicity following second dose suggests an immunity-boosting effect. Overall, these data may reduce negative attitudes towards COVID-19 vaccines.Study Registration.The study was registered on clinicaltrials.gov, NCT04402827.
    Keywords COVID-19 infection ; T-lymphocytes ; cell-mediated immunity ; cross reaction ; health services ; vaccination ; vaccines
    Language English
    Dates of publication 2021-1217
    Size p. 7367-7374.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2021.10.074
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    Zs.MO 458: Show issues

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  9. Article: Metabolic Snapshot of Plasma Samples Reveals New Pathways Implicated in SARS-CoV-2 Pathogenesis

    Albóniga, Oihane E. / Jiménez, Daniel / Sánchez-Conde, Matilde / Vizcarra, Pilar / Ron, Raquel / Herrera, Sabina / Martínez-Sanz, Javier / Moreno, Elena / Moreno, Santiago / Barbas, Coral / Serrano-Villar, Sergio

    Journal of proteome research. 2022 Feb. 08, v. 21, no. 3

    2022  

    Abstract: Despite the scientific and human efforts to understand COVID-19, there are questions still unanswered. Variations in the metabolic reaction to SARS-CoV-2 infection could explain the striking differences in the susceptibility to infection and the risk of ... ...

    Abstract Despite the scientific and human efforts to understand COVID-19, there are questions still unanswered. Variations in the metabolic reaction to SARS-CoV-2 infection could explain the striking differences in the susceptibility to infection and the risk of severe disease. Here, we used untargeted metabolomics to examine novel metabolic pathways related to SARS-CoV-2 susceptibility and COVID-19 clinical severity using capillary electrophoresis coupled to a time-of-flight mass spectrometer (CE-TOF-MS) in plasma samples. We included 27 patients with confirmed COVID-19 and 29 healthcare workers heavily exposed to SARS-CoV-2 but with low susceptibility to infection (“nonsusceptible”). We found a total of 42 metabolites of SARS-CoV-2 susceptibility or COVID-19 clinical severity. We report the discovery of new plasma biomarkers for COVID-19 that provide mechanistic explanations for the clinical consequences of SARS-CoV-2, including mitochondrial and liver dysfunction as a consequence of hypoxemia (citrulline, citric acid, and 3-aminoisobutyric acid (BAIBA)), energy production and amino acid catabolism (phenylalanine and histidine), and endothelial dysfunction and thrombosis (citrulline, asymmetric dimethylarginine (ADMA), and 2-aminobutyric acid (2-AB)), and we found interconnections between these pathways. In summary, in this first report several metabolic pathways implicated in SARS-CoV-2 susceptibility and COVID-19 clinical progression were found by CE-MS based metabolomics that could be developed as biomarkers of COVID-19.
    Keywords COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; amino acid metabolism ; biomarkers ; capillary electrophoresis ; citric acid ; citrulline ; disease severity ; energy ; health services ; histidine ; humans ; hypoxia ; liver ; metabolites ; metabolomics ; mitochondria ; pathogenesis ; phenylalanine ; proteome ; research ; risk ; spectrometers ; thrombosis
    Language English
    Dates of publication 2022-0208
    Size p. 623-634.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.1c00786
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  10. Article ; Online: mRNA-based SARS-CoV-2 Comirnaty vaccine elicits weak and short specific memory B cell response in individuals with no previous infection.

    Casado, José L / Vizcarra, Pilar / Martín-Hondarza, Adrián / Gómez-Maldonado, Sandra / Muedra-Sánchez, Magdalena / Del Pino, Judith / Mirabella, Itria G / Martín-Colmenarejo, Sara / Haemmerle, Johannes / Fernández-Escribano, Marina / Vallejo, Alejandro

    Frontiers in immunology

    2023  Volume 14, Page(s) 1127379

    Abstract: Objectives: The dynamics of the memory B cell (MBC) repertoire after SARS-CoV-2 vaccination is crucial for assessing long-term immunity. We compare spike-specific MBC responses between SARS-CoV-2 unexposed and recovered individuals, and their impact on ... ...

    Abstract Objectives: The dynamics of the memory B cell (MBC) repertoire after SARS-CoV-2 vaccination is crucial for assessing long-term immunity. We compare spike-specific MBC responses between SARS-CoV-2 unexposed and recovered individuals, and their impact on breakthrough infections during follow-up.
    Methods: Spike-specific MBC and T cells were quantified at inclusion and after two doses of mRNA vaccine in a longitudinal cohort of 85 naïve and 64 recovered participants (47 with positive serology and 17 with negative serology after infection).
    Results: At inclusion, there was minimal spike-specific MBC in naïve SARS-CoV-2 individuals. After the second vaccine dose, MBCs were significantly boosted in naïve individuals, but reached a significantly lower level than that observed even in unvaccinated SARS-CoV-2 convalescents (p<0.001). Furthermore, while the secondary memory B cell (MBC) population consisted of 100%, 33%, and 76% IgG
    Conclusions: MBCs were primed by mRNA-based vaccination in most cases, but SARS-CoV-2 naïve individuals had a blunted specific MBC response, and this was associated with a shorter time to breakthrough SARS-CoV-2 infection.
    MeSH term(s) Humans ; COVID-19 Vaccines ; COVID-19/prevention & control ; BNT162 Vaccine ; SARS-CoV-2 ; Memory B Cells ; RNA, Messenger/genetics ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M
    Chemical Substances COVID-19 Vaccines ; BNT162 Vaccine ; RNA, Messenger ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M
    Language English
    Publishing date 2023-06-29
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1127379
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