Memory T-Cell Responses to Vibrio cholerae O1 Infection

ABSTRACTVibrio choleraeO1 can cause diarrheal disease that may be life-threatening without treatment. Natural infection results in long-lasting protective immunity, but the role of T cells in this immune response has not been well characterized. In contrast, robust B-cell responses toV. choleraeinfection have been observed. In particular, memory B-cell responses to T-cell-dependent antigens persist for at least 1 year, whereas responses to lipopolysaccharide, a T-cell-independent antigen, wane more rapidly after infection. We hypothesize that protective immunity is mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue, and T-cell responses may be required to generate and maintain durable memory B-cell responses. In this study, we examined B- and T-cell responses in patients with severeV. choleraeinfection. Using the flow cytometric assay of the specific cell-mediated immune response in activated whole blood, we measured antigen-specific T-cell responses usingV. choleraeantigens, including the toxin-coregulated pilus (TcpA), aV. choleraemembrane preparation, and theV. choleraecytolysin/hemolysin (VCC) protein. Our results show that memory T-cell responses develop by day 7 after infection, a time prior to and concurrent with the development of B-cell responses. This suggests that T-cell responses toV. choleraeantigens may be important for the generation and stability of memory B-cell responses. The T-cell proliferative response to VCC was of a higher magnitude than responses observed to otherV. choleraeantigens.

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Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine

Clinical and Vaccine Immunology ◽

10.1128/cvi.00341-13 ◽

2013 ◽

Vol 20 (10) ◽

pp. 1541-1548 ◽

Cited By ~ 6

Author(s):

Mohammad Murshid Alam ◽

Daniel T. Leung ◽

Marjahan Akhtar ◽

Mohammad Nazim ◽

Sarmin Akter ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

T Cell Responses ◽

Memory B Cell ◽

Antibody Avidity ◽

Memory T Cell ◽

Cell Responses ◽

Specific Memory ◽

Iga Antibodies ◽

Specific Igg

ABSTRACTAntibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.

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Immunization with Live Attenuated Influenza Viruses That Express Altered NS1 Proteins Results in Potent and Protective Memory CD8+ T-Cell Responses

Journal of Virology ◽

10.1128/jvi.01317-09 ◽

2009 ◽

Vol 84 (4) ◽

pp. 1847-1855 ◽

Cited By ~ 31

Author(s):

Scott N. Mueller ◽

William A. Langley ◽

Elena Carnero ◽

Adolfo García-Sastre ◽

Rafi Ahmed

Keyword(s):

Influenza Virus ◽

T Cell ◽

B Cell ◽

Protective Immunity ◽

T Cell Responses ◽

Influenza Viruses ◽

Wild Type Virus ◽

Virus Infections ◽

Cell Responses ◽

B Cell Responses

ABSTRACT The generation of vaccines that induce long-lived protective immunity against influenza virus infections remains a challenging goal. Ideally, vaccines should elicit effective humoral and cellular immunity to protect an individual from infection or disease. Cross-reactive T- and B-cell responses that are elicited by live virus infections may provide such broad protection. Optimal induction of T-cell responses involves the action of type I interferons (IFN-I). Influenza virus expressed nonstructural protein 1 (NS1) functions as an inhibitor of IFN-I and promotes viral growth. We wanted to examine the priming of CD8+ T-cell responses to influenza virus in the absence of this inhibition of IFN-I production. We generated recombinant mouse-adapted influenza A/PR/8/34 viruses with NS1 truncations and/or deletions that also express the gp33-41 epitope from lymphocytic choriomeningitis virus. Intranasal infection of mice with the attenuated viruses primed long-lived T- and B-cell responses despite significantly reduced viral replication in the lungs compared to wild-type virus. Antigen-specific CD8+ T cells expanded upon rechallenge and generated increased protective memory T-cell populations after boosting. These results show that live attenuated influenza viruses expressing truncated NS1 proteins can prime protective immunity and may have implications for the design of novel modified live influenza virus vaccines.

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Persistence of antibody and T cell responses to the Sinopharm/BBIBP-CorV vaccine in Sri Lankan individuals

10.1101/2021.10.14.21265030 ◽

2021 ◽

Author(s):

Chandima Jeewandara ◽

Inoka Aberathna ◽

Pradeep Pushpakumara ◽

Achala Kamaladasa ◽

Dinuka Guruge ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

B Cell ◽

Severe Disease ◽

Age Groups ◽

T Cell Responses ◽

Sri Lankan ◽

Memory B Cell ◽

Cell Responses ◽

B Cell Responses

Background: To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP-CorV, we investigated immune responses in a cohort of Sri Lankan individuals. Methods: SARS-CoV-2 specific total antibodies were measured in 20-to-39 year (n=61), 40-to-59-year and those >60 years of age (n=22) by ELISA, 12 weeks after the second dose of the vaccine. ACE2 receptor blocking antibodies (ACE2R-Ab), antibodies to the receptor binding domain (RBD) of the ancestral virus (WT) and variants of concern, were measured in a sub cohort. T cell responses and memory B cell responses were assessed by ELISpot assays. Results: 193/203 (95.07%) of individuals had detectable SARS-CoV-2 specific total antibodies, while 67/110 (60.9%) had ACE2R-Ab. 14.3% to 16.7% individuals in the 20 to 39 age groups had detectable antibodies to the RBD of the WT and VOC, while the positivity rates of those >60 years of age was <10%. 14/49 (28.6%) had IFNγ ELISpot responses to overlapping peptides of the spike protein, while memory B cell responses were detected in 9/20 to the S1 recombinant protein. The total antibody levels and ACE2R-Ab declined after 2 to 12 weeks from the second dose, while ex vivo T cell responses remained unchanged. The decline in ACE2R-Ab levels was significant among the 40 to 59 (p=0.0007) and ≥60 (p=0.005) age groups. Conclusions: Antibody responses declined in all age groups, especially in those >60 years, while T cell responses persisted. The effect of waning of immunity on hospitalization and severe disease should be assessed by long term efficacy studies.

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The dichotomous and incomplete adaptive immunity in COVID-19 patients with different disease severity

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00525-3 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Leiqiong Gao ◽

Jing Zhou ◽

Sen Yang ◽

Lisha Wang ◽

Xiangyu Chen ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Adaptive Immunity ◽

Disease Severity ◽

Protective Immunity ◽

Rational Design ◽

T Cell Responses ◽

Cell Responses ◽

Asymptomatic Patients ◽

B Cell Responses

AbstractThe adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is elusive. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 64 patients with other disease severity (mild, n = 10, moderate, n = 32, severe, n = 12) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and prolonged humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results, therefore, uncovered the protective immunity in asymptomatic patients and also revealed the strikingly dichotomous and incomplete humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of effective COVID-19 vaccines.

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Elucidating T Cell and B Cell Responses to SARS-CoV-2 in Humans: Gaining Insights into Protective Immunity and Immunopathology

Cells ◽

10.3390/cells11010067 ◽

2021 ◽

Vol 11 (1) ◽

pp. 67

Author(s):

Aaruni Khanolkar

Keyword(s):

Immune Response ◽

T Cell ◽

B Cell ◽

Neutralizing Antibodies ◽

Protective Immunity ◽

Scientific Community ◽

Neutralizing Antibody ◽

Cell Responses ◽

Rapid Spread ◽

B Cell Responses

The SARS-CoV-2 pandemic is an unprecedented epochal event on at least two fronts. Firstly, in terms of the rapid spread and the magnitude of the outbreak, and secondly, on account of the equally swift response of the scientific community that has galvanized itself into action and has successfully developed, tested and deployed highly effective and novel vaccines in record time to combat the virus. The sophistication and diversification of the scientific toolbox we now have at our disposal has enabled us to interrogate both the breadth and the depth of the immune response to a degree that is unparalleled in recent memory. In terms of our understanding of what is critical to contain the virus and mitigate the effects the pandemic, neutralizing antibodies to SARS-CoV-2 garner most of the attention, however, it is essential to recognize that it is the quality and the fitness of the virus-specific T cell and B cell response that lays the foundation and the backdrop for an effective neutralizing antibody response. In this report, we will review some of the key findings that have helped define and delineate some of the essential attributes of T and B cell responses in the setting of SARS-CoV-2 infection.

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The dichotomous and incomplete adaptive immunity in COVID-19

10.1101/2020.09.05.20187435 ◽

2020 ◽

Cited By ~ 1

Author(s):

Leiqiong Gao ◽

Jing Zhou ◽

Sen Yang ◽

Xiangyu Chen ◽

Yang Yang ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Adaptive Immunity ◽

Disease Severity ◽

Protective Immunity ◽

Rational Design ◽

T Cell Responses ◽

Cell Responses ◽

Asymptomatic Patients ◽

B Cell Responses

The adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is also not well studied. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 49 patients with other disease severity (mild, n=10, moderate, n=32, severe, n=7) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and long-term humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results therefore uncovered the protective immunity in asymptomatic patients and revealed the strikingly dichotomous and unbalanced humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of COVID-19 vaccines.

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