scholarly journals Dynamics of immune recall following SARS-CoV-2 vaccination or breakthrough infection

2021 ◽  
Author(s):  
Marios Koutsakos ◽  
Wen Shi Lee ◽  
Arnold Reynaldi ◽  
Hyon-Xhi Tan ◽  
Grace Gare ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Viral Clearance ◽  
T Cell Immunity ◽  
Protective Effects ◽  
Breakthrough Infection ◽  
Humoral Immune ◽  
Cell Immunity ◽  
Antibody Titres ◽  
Longitudinal Sampling ◽  
Kinetics Of

Vaccination against SARS-CoV-2 results in protection from acquisition of infection as well as improved clinical outcomes even if infection occurs, likely reflecting a combination of residual vaccine-elicited immunity and the recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and T cell immunity after vaccination of seropositive individuals, and after breakthrough infection in vaccinated individuals. Intensive and early longitudinal sampling reveals the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titres. In breakthrough infections, the delayed kinetics of humoral immune recall provides a mechanism for the lack of early control of viral replication but likely underpins accelerated viral clearance and the protective effects of vaccination against severe COVID-19.

scholarly journals Antibody responses in buffalos immunized with Clostridium perfringens beta and epsilon toxoids

2001 ◽  
Vol 46 (No. 9–10) ◽  
pp. 241-243 ◽  
Author(s):  
S. Rahman M ◽  
K. Baek B ◽  
T. Hong S ◽  
H. Lee J
Keyword(s):  
Antibody Titre ◽  
Clostridium Perfringens ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Control Group ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Antibody Titres ◽  
Group A ◽  
And Control

The antibody responses to toxoids were measured to investigate whether Clostridium perfringens beta and epsilon toxoids induced protective humoral immune responses in buffalos. Total of 24 buffalos were divided into 4 groups (n = 6), beta toxoid, epsilon toxoid, combination and control groups. These buffalo groups were administered each of the designated toxoids. Immunizations in the beta and epsilon toxoid groups induced strong antibody responses. The neutralizing antibody titres from the beta and epsilon toxoid groups were equally log101.2 on day 21 after inoculation whereas there was no antibody titre detected from the control group. A statistically significant (P < 0.01) increase in antibody titre was observed from day 0 to day 14 and 21 after inoculation. The antibody production did not vary significantly due to day of inoculation and toxoid interactions.

scholarly journals Interleukin-1R Signaling Is Essential for Induction of Proapoptotic CD8 T Cells, Viral Clearance, and Pathology during Lymphocytic Choriomeningitis Virus Infection in Mice

2012 ◽  
Vol 86 (16) ◽  
pp. 8713-8719 ◽  
Author(s):  
Lars T. Joeckel ◽  
Reinhard Wallich ◽  
Sunil S. Metkar ◽  
Christopher J. Froelich ◽  
Markus M. Simon ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 1 ◽  
Lymphocytic Choriomeningitis ◽  
Lymphocytic Choriomeningitis Virus ◽  
Viral Clearance ◽  
T Cell Immunity ◽  
Cell Immunity ◽  
Deficient Mice

The T cell granule exocytosis pathway is essential to control hepatotropic lymphocytic choriomeningitis virus strain WE (LCMV-WE) but also contributes to the observed pathology in mice. Although effective antiviral T cell immunity and development of viral hepatitis are strictly dependent on perforin and granzymes, the molecular basis underlying induction of functionally competent virus-immune T cells, including participation of the innate immune system, is far from being resolved. We demonstrate here that LCMV-immune T cells of interleukin-1 receptor (IL-1R)-deficient mice readily express transcripts for perforin and granzymes but only translate perforin, resulting in the lack of proapoptotic potentialin vitro. LCMV is not cleared in IL-1R-deficient mice, and yet the infected mice develop neither splenomegaly nor hepatitis. These results demonstrate that IL-1R signaling is central to the induction of proapoptotic CD8 T cell immunity, including viral clearance and associated tissue injuries in LCMV infection.

scholarly journals 91. Differential Impact of Cytomegalovirus (CMV) Donor (D) Serostatus on Rates and Kinetics of CMV Viremia among CMV Seropositive Recipients (R+) of Ex vivo T-cell Depleted (TCD) and Unmodified (CONV) Hematopoietic Cell Transplants (HCT)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S7-S7
Author(s):  
Anat Stern ◽  
Yiqi Su ◽  
Jiaqi Fang ◽  
Miguel Perales ◽  
Molly Maloy ◽  
...  
Keyword(s):  
T Cell ◽  
Ex Vivo ◽  
Hematologic Malignancies ◽  
T Cell Immunity ◽  
Similar Frequency ◽  
Viral Loads ◽  
Cell Immunity ◽  
Cell Transplants ◽  
The Impact ◽  
Kinetics Of

Abstract Background In unmodified (CONV) HCT, CMV donor seropositivity (D+) conveys partial protection against CMV disease mediated by the transfer of donor CMV T-cell immunity through the allograft. Ex vivo T-cell depletion by CD34 selection affords a stringent depletion of donor T cells, thus transfer of donor T-cell immunity to CMV would be negligible. We evaluate the impact of CMV D serostatus on rates and kinetics of CMV viremia by Day (D)100 post-HCT in a contemporary cohort of CONV and TCD recipients from a single center. Methods A retrospective cohort study of R+ adult recipients of first peripheral blood or marrow HCT for hematologic malignancies (excluding multiple myeloma) from June 2010 to December 2017 at MSKCC. Routine CMV monitoring by a quantitative PCR assay occurred weekly from D14 through D100. Patients were treated preemptively. CMV viral burden was assessed as the time-averaged area under the viremia curve over 100 days from HCT (AAUC) calculated as the sum of the area of trapezoids of AUC viral loads divided by the number of weeks of follow-up viremia. The median AAUC for all patients with CMV reactivation (AAUC50) was used to classify patients as CMV controllers (AAUC ≤ AAUC50) or noncontrollers (AAUC >AAUC50). Results Of 509 R+, 290 (57%) patients received CONV and 219 (43%) TCD HCT; from 300 (59%) D+ and 209 (41%) D− donors. In CONV, CMV viremia occurred with similar frequency in D+ (65%) and D− (62%), P = 0.6. In contrast, in TCD, CMV viremia occurred more frequently in D+ compared with D− (83% vs. 71%, P = 0.03). Among CONV, D+ was associated with lower CMV burden (median AAUC) compared with D− (0.791 vs. 1.13, respectively, P = 0.0004). In contrast, in TCD, AAUC was similar between D− and D+ (1.19 vs. 1.35; P = 0.86). Among CONV with CMV viremia, D− were more likely to be noncontrollers compared with D+ (56% vs. 31%, respectively, P = 0.001). In contrast, among TCD with CMV viremia the proportion of noncontrollers was similar between D− and D+ (61% vs. 60%, respectively; P = 1). Conclusion Donor CMV serostatus has a differential effect on rates and kinetics of CMV viremia in R+ TCD and CONV HCT recipients. D+ is associated with less CMV viremia and less CMV burden in CONV but not in TCD. Our findings, if confirmed, have implications for donor selection algorithms. Disclosures All Authors: No reported Disclosures.

scholarly journals Loss of recognition of SARS-CoV-2 B.1.351 variant spike epitopes but overall preservation of T cell immunity

2021 ◽  
Author(s):  
Catherine Riou ◽  
Roanne Keeton ◽  
Thandeka Moyo-Gwete ◽  
Tandile Hermanus ◽  
Prudence Kgagudi ◽  
...  
Keyword(s):  
T Cell ◽  
Severe Disease ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Antibody Activity ◽  
Cell Responses ◽  
Cell Immunity ◽  
Fold Reduction

SARS-CoV-2 variants have emerged that escape neutralization and potentially impact vaccine efficacy. T cell responses play a role in protection from reinfection and severe disease, but the potential for spike mutations to affect T cell immunity is poorly studied. We assessed both neutralizing antibody and T cell responses in 44 South African COVID-19 patients infected either with B.1.351, now dominant in South Africa, or infected prior to its emergence (first wave), to provide an overall measure of immune evasion. We show for the first time that robust spike-specific CD4 and CD8 T cell responses were detectable in B.1.351-infected patients, similar to first wave patients. Using peptides spanning only the B.1.351 mutated regions, we identified CD4 T cell responses targeting the wild type peptides in 12/22 (54.5%) first wave patients, all of whom failed to recognize corresponding B.1.351-mutated peptides (p=0.0005). However, responses to the mutated regions formed only a small proportion (15.7%) of the overall CD4 response, and few patients (3/44) mounted CD8 responses that targeted the mutated regions. First wave patients showed a 12.7 fold reduction in plasma neutralization of B.1.351. This study shows that despite loss of recognition of immunodominant CD4 epitope(s), overall CD4 and CD8 T cell responses to B.1.351 are preserved. These observations may explain why, despite substantial loss of neutralizing antibody activity against B.1.351, several vaccines have retained the ability to protect against severe COVID-19 disease.

scholarly journals Potent Anti-Delta Effect By a Booster Third-Dose of UB-612, a Precision-Designed SARS-CoV-2 Multitope Protein-Peptide Vaccine

2021 ◽  
Author(s):  
Chang Yi wang ◽  
Kao-Pin Hwang ◽  
Hui-Kai Kuo ◽  
James Peng ◽  
Daphne Shen ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Phase 1 ◽  
Peptide Vaccine ◽  
Peptide Pool ◽  
T Cell Immunity ◽  
Breakthrough Infection ◽  
Clinical Phase ◽  
Cell Immunity ◽  
Waning Immunity

Abstract SARS-CoV-2 breakthrough infection occurs due to waning immunity time-to-vaccine, to which the globally-dominant, highly-contagious Delta variant is behind the scene. In the primary 2-dose and booster series of clinical Phase-1 trial, UB-612 vaccine, which contains S1-RBD and synthetic Th/CTL peptide pool for activation of humoral and T-cell immunity, induces substantial, prolonged viral-neutralizing antibodies that goes parallel with a long-lasting T-cell immunity; and a booster (3rd ) dose can prompt recall of memory immunity to induce profound, striking antibodies with the highest level of 50% viral-neutralizing GMT titers against live Delta variant reported for any vaccine. The unique design of S1-RBD only plus multitope T-cell peptides may have underpinned UB-612’s potent anti-Delta effect, while the other full S protein-based vaccines are affected additionally by mutations in the N-terminal domain sequence which contains additional neutralizing epitopes. UB-612, safe and well-tolerated, could be effective for boosting other vaccine platforms that have shown modest homologous boosting. [Funded by United Biomedical Inc., Asia; ClinicalTrials.gov ID: NCT04967742 and NCT04545749]

Immune responses of mice to inactivated rabies vaccine administered orally: potentiation by Quillaja saponin

1986 ◽  
Vol 32 (5) ◽  
pp. 414-420 ◽  
Author(s):  
I. Maharaj ◽  
K. J. Froh ◽  
J. B. Campbell
Keyword(s):  
Immune Responses ◽  
Oral Vaccine ◽  
Neutralizing Antibody ◽  
Rabies Vaccine ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Antibody Titres ◽  
The Many ◽  
Antibody Levels ◽  
Quillaja Saponin

Administered orally, Quillaja saponin markedly potentiated the humoral immune responses of mice fed inactivated rabies vaccine, and significantly increased their resistance to subsequent intracerebral challenge with live rabies virus. Although mean serum neutralizing antibody titres were generally 8- to 16-fold higher when vaccine was given intraperitoneally, orally administered vaccine, with saponin, stimulated production of high protective antibody levels that were maintained for at least 6 months. The potentiating effect of saponin appeared to be mediated through several mechanisms, one of which was by increasing the permeability of the intestinal mucosa, allowing increased uptake of viral antigen. The potentiating effect was enhanced when saponin was administered in advance (up to at least 16 h) of the oral vaccine. Mice tolerated the effective saponin doses without any visible signs of distress or injury. In view of the many favourable physiological activities and low toxicity of orally delivered saponins, it is suggested that they may find more general applications in the immunopotentiation of oral vaccines.

scholarly journals Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lana Vandersarren ◽  
Cedric Bosteels ◽  
Manon Vanheerswynghels ◽  
James J. Moon ◽  
Andrew J. Easton ◽  
...  
Keyword(s):  
T Cell ◽  
Epitope Mapping ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
Cell Immunity ◽  
Kinetics Of

scholarly journals Delayed interval BNT162b2 mRNA COVID-19 vaccination provides robust immunity

2021 ◽  
Author(s):  
Victoria Hall ◽  
Victor Ferreira ◽  
Matthew Ierullo ◽  
Terrance Ku ◽  
Beata Majchrzak-Kita ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Neutralizing Antibody ◽  
Interferon Γ ◽  
Interval Group ◽  
Standard Interval ◽  
Humoral Immune ◽  
Antibody Titres ◽  
Delayed Group ◽  
Cellular Immune

Abstract Shortages of COVID-19 vaccines have results in delayed dosing intervals as a strategy to immunize a greater proportion of the population. The effect of this strategy on vaccine immunogenicity is not well studied. Humoral (anti-RBD levels and neutralization) and cellular immune responses were compared in health care workers receiving two doses of BNT162b2 (Pfizer-BioNTech) vaccines at standard (3-6 week) and delayed (8-12 week) intervals. In the delayed group, anti-RBD antibody titres were significantly enhanced compared to the standard interval group. Neutralizing antibody responses were excellent and comparable in both groups. A slight decrease in Spike-specific polyfunctional CD4+ T-cells expressing interferon-γ and IL-2 as well as monofunctional CD4+ T-cells was seen in the delayed group. Both polyfunctional and monofunctional CD8+ T-cell responses were comparable. Our data suggest that the strategy of delayed second dose mRNA vaccination is not overtly detrimental, and specifically may lead to an enhanced humoral immune response.

scholarly journals Vaccine-Induced Measles Virus-Specific T Cells Do Not Prevent Infection or Disease but Facilitate Subsequent Clearance of Viral RNA

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Wen-Hsuan W. Lin ◽  
Chien-Hsiung Pan ◽  
Robert J. Adams ◽  
Beth L. Laube ◽  
Diane E. Griffin
Keyword(s):  
T Cells ◽  
T Cell ◽  
Measles Virus ◽  
Neutralizing Antibody ◽  
T Cell Immunity ◽  
Viral Rna ◽  
Measles Vaccine ◽  
Wild Type ◽  
Cell Responses ◽  
Cell Immunity

ABSTRACTInfection with wild-type measles virus (MeV) induces lifelong protection from reinfection, and parenteral delivery of the live attenuated measles vaccine (LAV) also provides protection from measles. The level of neutralizing antibody is a good indicator of protection, but the independent roles of MeV-specific antibody and T cells have not been identified. In this study, macaques immunized with LAV through a nebulizer and a mouthpiece developed MeV-specific T-cell responses but not neutralizing antibodies. Upon challenge with wild-type MeV, these animals developed rashes and viremias similar to those in naive animals but cleared viral RNA from blood 25 to 40 days faster. The nebulizer-immunized animals also had more robust MeV-specific CD4+and CD8+T-cell responses than the naive animals after challenge, characterized by a higher number and better durability of gamma interferon (IFN-γ)-producing cells. Induction of MeV-specific circulating CD4+and CD8+T cells capable of producing multiple cytokines correlated with clearance of viral RNA in the nebulizer-immunized macaques. These studies demonstrated that MeV-specific T-cell immunity alone did not prevent measles, but T-cell priming enhanced the magnitude, durability, and polyfunctionality of MeV-specific T cells after challenge infection and correlated with more rapid clearance of MeV RNA.IMPORTANCEThe components of vaccine-induced immunity necessary for protection from infection and disease have not been clearly identified for most vaccines. Vaccine development usually focuses on induction of antibody, but T-cell-based vaccines are also under development. The live attenuated measles vaccine (LAV) given subcutaneously induces both T cells and neutralizing antibody and provides solid protection from infection. LAV delivered to the upper respiratory tract through a nebulizer and mouthpiece induced a T-cell response but no neutralizing antibody. These T-cell-primed macaques demonstrated no protection from rash or viremia when challenged with wild-type MeV, but viral RNA was cleared more rapidly than in unimmunized animals. Thus, T-cell immunity did not protect from infection or acute disease but facilitated virus clearance during recovery. These studies demonstrate the importance and independent roles of T cells and antibody in protection and recovery from measles.

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