scholarly journals A Novel LNP-based Chlamydia subunit vaccine formulation that induces Th1 responses without upregulating IL-17 provides equivalent protection in mice as formulations that induced IL-17 and Th1 cytokines

2019 ◽  
Author(s):  
Melissa Ann Boddicker ◽  
Robin M. Kaufhold ◽  
Kara S. Cox ◽  
Bob J. Lucas ◽  
Jinfu Xie ◽  
...  
Keyword(s):  
T Cell ◽  
Membrane Protein ◽  
Lipid A ◽  
T Cell Responses ◽  
Control Group ◽  
Cell Responses ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Antibody Titers ◽  
Dimethyldioctadecylammonium Bromide

Abstract Sexually transmitted Chlamydia infections can lead to the development of debilitating diseases such as chronic pelvic pain, ectopic pregnancy, pelvic inflammatory disease, and infertility. It has been proposed that immunity against Chlamydia infection and disease may be determined by a balance of IL-17 signaling. We sought to evaluate novel formulations for a candidate Chlamydia vaccine, consisting of Chlamydia major outer membrane protein (MOMP) alone or in combination with polymorphic membrane protein D (PmpD) and polymorphic membrane protein G (PmpG) as target immunogens. Native MOMP (nMOMP) isolated from C. muridarum elementary bodies (EBs) and recombinant PmpD and PmpG proteins were adjuvanted with Monophosphoryl lipid A (MPLA), in one of two formulations containing either lipid nanoparticles (LNPs) or the cationic lipid dimethyldioctadecylammonium bromide (DDA). Antibody titers to C. muridarum, nMOMP, and EBs were evaluated by ELISA, and T-cell responses by intracellular cytokine staining (ICS). Protection from challenge was determined by qPCR and gross pathology. All mice immunized with the new vaccine formulations showed significantly higher antibody titers to nMOMP (P<0.001) and C. muridarum EBs (P<0.001), when compared to the negative control group (adjuvant alone). Antibody titers in vaccine groups with Monophosphoryl lipid A (MPLA)+LNP were higher as compared to the MPLA+DDA group (P<0.001) except for groups 6 (Cm nMOMP+PmpG+PmpD p73+PmpD p82+MPLA+DDA) vs 7 (Cm nMOMP+PmpG+PmpD p73+PmpD p82+MPLA+LNP) for both C. muridarum EBs and PmpG; the groups were not statistically significant. ICS analysis showed more robust CD4+ T-cell responses (IFN-γ/IL-2/TNF-α) in the dimethyldioctadecylammonium bromide (DDA) and LNP groups compared to the adjuvant alone group. The combination of DDA and MPLA gave robust Th17 responses in comparison to MPLA and LNP group. Immunized groups also showed protection from challenge with C. muridarum , as evidenced by a reduction in bacterial shedding from the vagina for all groups (P<0.003) compared to shedding from the adjuvant control, Group 1. Both vaccine formulations generated robust immunological responses and both vaccine formulations were protective by reducing bacterial shedding after challenge. This data indicates equal protection can be achieved without the induction of Th17 responses.

Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers

Vaccine ◽  
2008 ◽  
Vol 26 (10) ◽  
pp. 1375-1386 ◽  
Author(s):  
Pierre Vandepapelière ◽  
Yves Horsmans ◽  
Philippe Moris ◽  
Marcelle Van Mechelen ◽  
Michel Janssens ◽  
...  
Keyword(s):  
T Cell ◽  
Hepatitis B ◽  
Lipid A ◽  
Healthy Adult ◽  
Hepatitis B Surface Antigen ◽  
Vaccine Adjuvant ◽  
Cell Responses ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Adult Volunteers

scholarly journals Comparison of humoral and cellular responses in kidney transplant recipients receiving BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines

2021 ◽  
Author(s):  
Maria Prendecki ◽  
Tina Thomson ◽  
Candice L Clarke ◽  
Paul Martin ◽  
Sarah Gleeson ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
T Cell Responses ◽  
Cellular Responses ◽  
Control Group ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cell Responses ◽  
Transplant Patients ◽  
Kidney Transplant Patients

Background Attenuated immune responses to mRNA SARS-CoV-2 vaccines have been reported in solid organ transplant recipients. Most studies have assessed serological responses alone, and there is limited immunological data on vector-based vaccines in this population. This study compares the immunogenicity of BNT162b2 with ChAdOx1 in kidney transplant patients, assessing both serological and cellular responses. Methods 920 patients were screened for spike protein antibodies (anti-S) following 2 doses of either BNT162b2 (n=490) or ChAdOx1 (n=430). 106 patients underwent assessment with T-cell ELISpot assays. 65 health care workers were used as a control group. Results Anti-S was detected in 569 (61.8%) patients. Seroconversion rates in infection-naïve patients who received BNT162b2 were higher compared with ChAdOx1, at 269/410 (65.6%) and 156/358 (43.6%) respectively, p<0.0001. Anti-S concentrations were higher following BNT162b, 58(7.1-722) BAU/ml, compared with ChAdOx1, 7.1(7.1-39) BAU/ml, p<0.0001. Calcineurin inhibitor monotherapy, vaccination occurring >1st year post-transplant and receiving BNT162b2 was associated with seroconversion. Only 28/106 (26.4%) of patients had detectable T-cell responses. There was no difference in detection between infection-naïve patients who received BNT162b2, 7/40 (17.5%), versus ChAdOx1, 2/39 (5.1%), p=0.15. There was also no difference in patients with prior infection who received BNT162b2, 8/11 (72.7%), compared with ChAdOx1, 11/16 (68.8%), p=0.83. Conclusions. Enhanced humoral responses were seen with BNT162b2 compared with ChAdOx1 in kidney transplant patients. T-cell responses to both vaccines were markedly attenuated. Clinical efficacy data is still required but immunogenicity data suggests weakened responses to both vaccines in transplant patients, with ChAdOx1 less immunogenic compared with BNT162b2.

scholarly journals High Frequencies of Functional Virus-Specific CD4+ T Cells in SARS-CoV-2 Subjects With Olfactory and Taste Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Dalila Mele ◽  
Anna Calastri ◽  
Eugenia Maiorano ◽  
Antonella Cerino ◽  
Michele Sachs ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
T Cell Responses ◽  
Control Group ◽  
Presenting Symptoms ◽  
Cell Responses ◽  
Taste Disorders ◽  
Specific Igg

Olfactory and taste disorders (OTD) are commonly found as presenting symptoms of SARS-CoV-2 infection in patients with clinically mild COVID-19. Virus-specific T cells are thought to play an important role in the clearance of SARS-CoV-2; therefore the study of T cell specific immune responses in patients with mild symptoms may help to understand their possible role in protection from severe disease. We evaluated SARS-CoV-2-specific T cell responses to four different peptide megapools covering all SARS-CoV-2 proteins during the acute phase of the disease in 33 individuals with mild or no other symptom beside OTD and in 22 age-matched patients with severe infection. A control group of 15 outpatients with OTD and consistently negative nasopharyngeal SARS-CoV-2 RNA swabs and virus-specific IgG serology was included in the study. Increased frequencies of virus-specific CD4+ and CD8+ T cells were found in SARS-CoV-2 positive patients with OTD compared with those with severe COVID-19 and with SARS-CoV-2 negative OTD individuals. Moreover, enhanced CD4+ and CD8+ T-cell activation induced by SARS-CoV-2 peptides was associated with higher interferon (IFN)γ production. Increased frequencies of Spike (S1/S2)-specific CD4+ T cells showing enhanced IFNγ secretion and granzyme B content were associated with serum spike-specific IgG in the OTD group. In conclusion, patients with SARS-CoV-2 induced OTD develop highly functional virus-specific CD4+ and CD8+ T cells during the symptomatic phase of the disease, suggesting that robust and coordinated T-cell responses provide protection against extension of COVID-19 to the lower respiratory tract.

Phase II Randomized Study of Vaccine Treatment of Advanced Prostate Cancer (E7897): A Trial of the Eastern Cooperative Oncology Group

2004 ◽  
Vol 22 (11) ◽  
pp. 2122-2132 ◽  
Author(s):  
Howard L. Kaufman ◽  
Wei Wang ◽  
Judith Manola ◽  
Robert S. DiPaola ◽  
Yoo-Joung Ko ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
T Cell ◽  
Phase Ii ◽  
Eastern Cooperative Oncology Group ◽  
T Cell Responses ◽  
Oncology Group ◽  
Clinical Progression ◽  
Cell Responses ◽  
Antibody Titers

Purpose A phase II clinical trial was conducted to evaluate the feasibility and tolerability of a prime/boost vaccine strategy using vaccinia virus and fowlpox virus expressing human prostate-specific antigen (PSA) in patients with biochemical progression after local therapy for prostate cancer. The induction of PSA-specific immunity was also evaluated. Patients and Methods A randomized clinical trial was conducted by the Eastern Cooperative Oncology group and 64 eligible patients were randomly assigned to receive four vaccinations with fowlpox-PSA (rF-PSA), three rF-PSA vaccines followed by one vaccinia-PSA (rV-PSA) vaccine, or one rV-PSA vaccine followed by three rF-PSA vaccines. The major end point was PSA response at 6 months, and immune monitoring included measurements of anti-PSA and anti-vaccinia antibody titers and PSA-specific T-cell responses. Results The prime/boost schedule was well tolerated with few adverse events. Of the eligible patients, 45.3% of men remained free of PSA progression at 19.1 months and 78.1% demonstrated clinical progression-free survival. There was a trend favoring the treatment group that received a priming dose of rV-PSA. Although no significant increases in anti-PSA antibody titers were detected, 46% of patients demonstrated an increase in PSA-reactive T-cells. Conclusion Therapy with poxviruses expressing PSA and delivered in a prime/boost regimen was feasible and associated with minimal toxicity in the cooperative group setting. A significant proportion of men remained free of PSA and clinical progression after 19 months follow-up, and nearly half demonstrated an increase in PSA-specific T-cell responses. Phase III studies are needed to define the role of vaccination in men with prostate cancer or those who are at risk for the disease.

scholarly journals The Combinations Chitosan-Pam3CSK4 and Chitosan-Monophosphoryl Lipid A: Promising Immune-Enhancing Adjuvants for Anticaries Vaccine PAc

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Yongli Bi ◽  
Qingan Xu ◽  
Lingkai Su ◽  
Jiantao Xu ◽  
Zhongfang Liu ◽  
...  
Keyword(s):  
Lipid A ◽  
Vaccine Development ◽  
Protection Effect ◽  
Content Type ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Tooth Surfaces ◽  
Antibody Titers

ABSTRACT We previously demonstrated that recombinant protein PAc could be administered as an anticaries vaccine. However, the relatively weak immunogenicity of PAc limits its application. In the present study, we investigated the effect of two adjuvant combinations of chitosan plus Pam3CSK4 (chitosan-Pam3CSK4) and of chitosan plus monophosphoryl lipid A (chitosan-MPL) in the immune responses to the PAc protein in vivo and in vitro. PAc-chitosan-Pam3CSK4 or PAc-chitosan-MPL promoted significantly higher PAc-specific antibody titers in serum and saliva, inhibited Streptococcus mutans colonization onto the tooth surfaces, and endowed better protection effect with significantly less caries activities than PAc alone. Chitosan-Pam3CSK4 and chitosan-MPL showed no statistically significant differences. In conclusion, our study demonstrated that the chitosan-Pam3CSK4 and chitosan-MPL combinations are promising for anticaries vaccine development.

scholarly journals Novel Epstein-Barr virus-like particles incorporating gH/gL-EBNA1 or gB-LMP2 induce high neutralizing antibody titers and EBV-specific T-cell responses in immunized mice

Oncotarget ◽  
2016 ◽  
Vol 8 (12) ◽  
pp. 19255-19273 ◽  
Author(s):  
Elizabeth M. Perez ◽  
Joslyn Foley ◽  
Timelia Tison ◽  
Rute Silva ◽  
Javier Gordon Ogembo
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Virus Like Particles ◽  
Barr Virus ◽  
Cell Responses ◽  
Antibody Titers ◽  
Epstein Barr

scholarly journals Induction of EBV–Latent Membrane Protein 1–Specific MHC Class II–Restricted T-Cell Responses against Natural Killer Lymphoma Cells

2008 ◽  
Vol 68 (3) ◽  
pp. 901-908 ◽  
Author(s):  
Hiroya Kobayashi ◽  
Toshihiro Nagato ◽  
Miki Takahara ◽  
Keisuke Sato ◽  
Shoji Kimura ◽  
...  
Keyword(s):  
T Cell ◽  
Membrane Protein ◽  
Natural Killer ◽  
Mhc Class Ii ◽  
T Cell Responses ◽  
Class Ii ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 1 ◽  
Lymphoma Cells ◽  
Cell Responses

scholarly journals Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C

2016 ◽  
Vol 90 (23) ◽  
pp. 10459-10471 ◽  
Author(s):  
Cibele M. Gaido ◽  
Shane Stone ◽  
Abha Chopra ◽  
Wayne R. Thomas ◽  
Peter N. Le Souëf ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Antibody Responses ◽  
T Cell Proliferation ◽  
T Cell Epitopes ◽  
Future Studies ◽  
Cell Responses ◽  
Asthma Exacerbations ◽  
Antibody Titers ◽  
Vp1 Capsid Protein

ABSTRACTRhinovirus (RV) species A and C are the most frequent cause of respiratory viral illness worldwide, and RV-C has been linked to more severe exacerbations of asthma in young children. Little is known about the immune responses to the different RV species, although studies comparing IgG1 antibody titers found impaired antibody responses to RV-C. Therefore, the aim of this study was to assess whether T-cell immunity to RV-C is similarly impaired. We measured T-cell proliferation to overlapping synthetic peptides covering the entire VP1 capsid protein of an RV-A and RV-C genotype for 20 healthy adult donors. Human leukocyte antigen (HLA) was typed in all the donors in order to investigate possible associations between the HLA type and RV peptide recognition. Total and specific IgG1 antibody titers to the VP1 proteins of both RV-A and RV-C were also measured to examine associations between the antibody and T-cell responses. We identified T-cell epitopes that are specific to and representative of each RV-A and RV-C species. These epitopes stimulated CD4+-specific T-cell proliferation, with similar magnitudes of response for both RV species. All the donors, independent of their HLA-DR or -DQ type, were able to recognize the immunodominant RV-A and -C regions of VP1. Furthermore, the presence or absence of specific antibody titers was not related to changes in T-cell recognition. Our results indicate a dissociation between the antibody and T-cell responses to rhinoviruses. The species-representative T-cell epitopes identified in this study are valuable tools for future studies investigating T-cell responses to the different RV species.IMPORTANCERhinoviruses (RVs) are mostly associated with the common cold and asthma exacerbations, although their contributions to most upper and lower respiratory tract diseases have increasingly been reported. Species C (RV-C) has been associated with more frequent and severe asthma exacerbations in young children and, along with RV-A, is the most clinically relevant species. Little is known about how our immune system responds to rhinoviruses, and there are limited tools to study specific adaptive immunity against each rhinovirus species. In this study, we identified immunodominant T-cell epitopes of the VP1 proteins of RV-A and RV-C, which are representative of each species. The study found that T-cell responses to RV-A and RV-C were of similar magnitudes, in contrast with previous findings showing RV-C-specific antibody responses were low. These findings will provide the basis for future studies on the immune response to rhinoviruses and can help elucidate the mechanisms of severity of rhinovirus-induced infections.

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