T cell response to rat urinary protein in sensitised and non sensitised individuals and a non exposed control group

A vaccine against congenital cytomegalovirus infection is a high priority. Guinea pig cytomegalovirus (GPCMV) is the only congenital CMV small animal model. GPCMV encodes essential glycoprotein complexes for virus entry (gB, gH/gL/gO, gM/gN) including a pentamer complex (gH/gL/GP129/GP131/GP133 or PC) for endocytic cell entry. The cohorts for protection against congenital CMV are poorly defined. Neutralizing antibodies to the viral glycoprotein complexes are potentially more important than an immunodominant T-cell response to the pp65 protein. In GPCMV, GP83 (pp65 homolog) is an evasion factor, and the GP83 mutant GPCMV has increased sensitivity to type I interferon. Although GP83 induces a cell-mediated response, a GP83-only-based vaccine strategy has limited efficacy. GPCMV attenuation via GP83 null deletion mutant in glycoprotein PC positive or negative virus was evaluated as live-attenuated vaccine strains (GP83dPC+/PC-). Vaccinated animals induced antibodies to viral glycoprotein complexes, and PC+ vaccinated animals had sterilizing immunity against wtGPCMV challenge. In a pre-conception vaccine (GP83dPC+) study, dams challenged mid-2nd trimester with wtGPCMV had complete protection against congenital CMV infection without detectable virus in pups. An unvaccinated control group had 80% pup transmission rate. Overall, gB and PC antibodies are key for protection against congenital CMV infection, but a response to pp65 is not strictly necessary.

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Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients

Clinical Research in Cardiology ◽

10.1007/s00392-021-01880-5 ◽

2021 ◽

Author(s):

René Schramm ◽

Angelika Costard-Jäckle ◽

Rasmus Rivinius ◽

Bastian Fischer ◽

Benjamin Müller ◽

...

Keyword(s):

T Cell ◽

Cell Response ◽

Messenger Rna ◽

Neutralizing Antibodies ◽

Cellular Response ◽

T Cell Response ◽

Control Group ◽

Immunocompromised Patients ◽

Transplant Recipients ◽

Transplant Patients

Abstract Aims Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients. Methods and results A total of 50 transplant patients [1–3 years post heart (42), lung (7), or heart–lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness. Conclusions The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.

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Evidence of extensive cellular immune response after SARS-CoV-2 vaccination in ocrelizumab-treated patients with multiple sclerosis

Neurological Research and Practice ◽

10.1186/s42466-021-00158-5 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Mosche Pompsch ◽

Neslinur Fisenkci ◽

Peter A. Horn ◽

Markus Kraemer ◽

Monika Lindemann

Keyword(s):

Multiple Sclerosis ◽

T Cell ◽

B Cell ◽

Cell Response ◽

Humoral Response ◽

T Cell Response ◽

Control Group ◽

Partial Protection ◽

Cellular Immune ◽

Age And Sex

Abstract Background Patients with multiple sclerosis receiving ocrelizumab-treatment are in desperate need of a protection against SARS-CoV-2 infection. Methods In this study, Euroimmun semi-quantitative Anti-SARS-CoV-2 IgG for detection of humoral response and ELISpot assays for detection of SARS-CoV-2-specific T-cell-response were used in 10 ocrelizumab-treated patients with multiple sclerosis twice vaccinated with Comirnaty® mRNA vaccine. This data was compared with a control group of 20 age- and sex-matched healthy volunteers, who had all previously received a full SARS-CoV-2 mRNA vaccination with Comirnaty® or Spikevax®. Results While all subjects in the control group had high humoral response to the vaccination, in B-cell-depleted individuals a significantly reduced antibody response to vaccination against SARS-CoV-2 was observed. SARS-CoV-2 specific T-cell-response, however, did not differ significantly between both cohorts. Conclusions T-cell-mediated response to Comirnaty® vaccination is observable despite attenuated humoral response in B-cell-depleted patients. This might enable partial protection against COVID-19. Trial registration Retrospectively registered.

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