Peripheral CD4 T follicular cells induced by a conjugated pneumococcal vaccine correlate with enhanced opsonophagocytic antibody responses in younger individuals

Peng, Binghao J.; Burton, Robert L.; LaFon, David C.; Westfall, Andrew O.; Singh, Suddham; Pride, Michael W.; Anderson, Annaliesa S.; Ippolito, Gregory C.; Schroeder, Harry W.; Nahm, Moon H.; Prasad, A. Krishna; Goepfert, Paul; Bansal, Anju

doi:10.1016/j.vaccine.2019.12.023

Cited by 25 publications

(19 citation statements)

References 47 publications

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“…We next investigated any correlations of age and frequency of activation and exhaustion markers in the non-hospitalized group. Our group and others have reported that elderly individuals form suboptimal immune responses following vaccination and infection (43). In this study, within the CD4+ T-cell compartment, we observed increased frequencies of PD1, TIGIT, and HLA-DR that correlated positively with age ( Figure 7A-C, p=0.002, p=0.032 and p=0.022, respectively).…”

Section: Individualssupporting

confidence: 66%

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection

Files¹,

Boppana²,

Perez³

et al. 2021

Journal of Clinical Investigation

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122

108

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SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and non-hospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared to healthy and convalescent individuals, with the exception of B lymphocytes which increased. Our findings show increased frequencies of T-cell activation markers (CD69, OX40, HLA-DR and CD154) in hospitalized patients, with other T-cell activation/exhaustion markers (PD-L1 and TIGIT) remaining elevated in hospitalized and nonhospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization, followed by an increase in PD1 frequencies in non-hospitalized individuals. Interestingly, many of these changes were found to increase over time in non-hospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation following SARS-CoV-2 infection. Changes in T-cell activation/exhaustion in nonhospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation following SARS-CoV-2 infection highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.

show abstract

Section: Individualssupporting

confidence: 66%

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection

Files¹,

Boppana²,

Perez³

et al. 2021

Journal of Clinical Investigation

Self Cite

122

108

View full text Add to dashboard Cite

show abstract

“…We next investigated any correlations of age and frequency of activation and exhaustion markers in the non-hospitalized group. Our group and others have reported that elderly individuals form suboptimal immune responses following vaccination and infection (44). In this study, within the CD4+ T-cell compartment, we observed increased frequencies of PD1, TIGIT, and HLA-DR that correlated positively with age ( Figure 7A-C , p=0.002, p=0.032 and p=0.022, respectively).…”

Section: Resultsmentioning

confidence: 96%

Sustained Cellular Immune Dysregulation in Individuals Recovering from SARS-CoV-2 Infection

Files

Boppana

Perez

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and non-hospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared to healthy and convalescent individuals, with the exception of B lymphocytes which increased. Our findings show increased frequencies of T-cell activation markers (CD69, Ox40, HLA-DR and CD154) in hospitalized patients, with other T-cell activation/exhaustion markers (CD25, PD-L1 and TIGIT) remaining elevated in hospitalized and non-hospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization, followed by an increase in PD1 frequencies in non-hospitalized individuals. Interestingly, many of these changes were found to increase over time in non-hospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation following SARS-CoV-2 infection. Changes in T-cell activation/exhaustion in non-hospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation following SARS-CoV-2 infection highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.

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Section: Introductionmentioning

confidence: 99%

“…While frequencies of circulating CXCR5 + PD1 + CD4 T cells are typically low, these cells are closely linked to Tfh in lymphoid tissue (19) and have been shown to support humoral responses (20,21). Antigen-specific pTfh have been shown to correlate with neutralizing antibodies in the context of infection and vaccination of several pathogens (17,(22)(23)(24)(25)(26). Although pTfh responses have not been described in the context of SARS-CoV or MERS-CoV infection, CD4 T-cell responses have been shown to be important in controlling SARS-CoV in mouse models (27), and a recent study of a MERS-CoV vaccine in mice found that Tfh frequencies in draining lymph nodes correlated with neutralizing antibodies (28).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2-specific peripheral T follicular helper cells correlate with neutralizing antibodies and increase during convalescence

Boppana

Files

Russell

et al. 2020

Preprint

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T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 21 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mount at least one CD4 T-cell response, and 48% of individuals mount detectable SARS-CoV-2-specific peripheral T follicular helper cells (pTfh, defined as CXCR5+PD1+ CD4 T cells). SARS-CoV-2-specific pTfh responses across all three protein specificities correlate with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, pTfh responses increase in frequency and magnitude in convalescence, and robust responses with magnitudes greater than 5% were detected only at the second convalescent visit, an average of 38 days post-symptom onset. These data deepen our understanding of antigen-specific pTfh responses in SARS-CoV-2 infection, suggesting that M and N protein-specific pTfh may also assist in the development of neutralizing antibodies and that pTfh response formation may be delayed in SARS-CoV-2 infection.

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Peripheral CD4 T follicular cells induced by a conjugated pneumococcal vaccine correlate with enhanced opsonophagocytic antibody responses in younger individuals

Cited by 25 publications

References 47 publications

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection

Sustained Cellular Immune Dysregulation in Individuals Recovering from SARS-CoV-2 Infection

SARS-CoV-2-specific peripheral T follicular helper cells correlate with neutralizing antibodies and increase during convalescence

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