Virus and virus-like particle-based immunogens for Alzheimer's disease induce antibody responses against amyloid-β without concomitant T cell responses

The immune response induced by immunization with HIV Env DNA and virus-like particle (VLP) vaccines was investigated. Immunization with the HIV Env DNA vaccine induced a strong CD8 T cell response but relatively weak antibody response against the HIV Env whereas immunization with VLPs induced higher levels of antibody responses but little CD8 T cell response. Interestingly, immunization with a mixture the HIV Env DNA and VLP vaccines induced enhanced CD8 T cell and antibody responses. Further, it was observed that the mixing of DNA and VLP vaccines during immunization is necessary for augmenting induction of CD8 T cell responses and such augmentation of CD8 T cell responses was also observed by mixing the HIV Env DNA vaccine with control VLPs. These results show that immunization with a mixture of DNA and VLP vaccines combines advantages of both vaccine platforms for eliciting high levels of both antibody and CD8 T cell responses.

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T Cell Responses to Neural Autoantigens Are Similar in Alzheimer’s Disease Patients and Age-Matched Healthy Controls

Frontiers in Neuroscience ◽

10.3389/fnins.2020.00874 ◽

2020 ◽

Vol 14 ◽

Author(s):

Rekha Dhanwani ◽

John Pham ◽

Ashmitaa Logandha Ramamoorthy Premlal ◽

April Frazier ◽

Atul Kumar ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

T Cell ◽

T Cell Responses ◽

Healthy Controls ◽

Cell Responses

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O2-03-01: Beta-amyloid-specific CD4+ T cell responses change with age and Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.634 ◽

2012 ◽

Vol 8 (4S_Part_7) ◽

pp. P239-P239

Author(s):

Doug Ethell ◽

Aynun Begum ◽

Celia Cunha ◽

Harpreet Sidhu ◽

Tursun Alkam

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

T Cell ◽

T Cell Responses ◽

Beta Amyloid ◽

Cd4 T Cell ◽

Cell Responses

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Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses

Journal of Experimental Medicine ◽

10.1084/jem.20170161 ◽

2017 ◽

Vol 214 (9) ◽

pp. 2563-2572 ◽

Cited By ~ 9

Author(s):

Spencer W. Stonier ◽

Andrew S. Herbert ◽

Ana I. Kuehne ◽

Ariel Sobarzo ◽

Polina Habibulin ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

Ebola Virus ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Cd8 T Cell ◽

Marburg Virus ◽

Antibody Responses ◽

Cd4 T Cell ◽

Cell Responses

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity.

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MHC-Independent Genetic Factors Control the Magnitude of CD4+ T Cell Responses to Amyloid-β Peptide in Mice through Regulatory T Cell-Mediated Inhibition

The Journal of Immunology ◽

10.4049/jimmunol.1003953 ◽

2011 ◽

Vol 187 (9) ◽

pp. 4492-4500 ◽

Cited By ~ 13

Author(s):

Cécile Toly-Ndour ◽

Gabrielle Lui ◽

Maria Manuel Nunes ◽

Martine Bruley-Rosset ◽

Pierre Aucouturier ◽

...

Keyword(s):

T Cell ◽

Regulatory T Cell ◽

Genetic Factors ◽

Amyloid Β ◽

T Cell Responses ◽

Cd4 T Cell ◽

Amyloid Β Peptide ◽

Cell Responses

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Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses

Vaccines ◽

10.3390/vaccines8010004 ◽

2019 ◽

Vol 8 (1) ◽

pp. 4 ◽

Cited By ~ 9

Author(s):

Muktha S. Natrajan ◽

Nadine Rouphael ◽

Lilin Lai ◽

Dmitri Kazmin ◽

Travis L. Jensen ◽

...

Keyword(s):

Gene Expression ◽

T Cell ◽

Immune Responses ◽

T Cell Responses ◽

Innate Immune ◽

Antibody Responses ◽

Cytokine Signaling ◽

Cell Responses ◽

Viral Vaccine ◽

Tularemia Vaccine

Background: Tularemia is a potential biological weapon due to its high infectivity and ease of dissemination. This study aimed to characterize the innate and adaptive responses induced by two different lots of a live attenuated tularemia vaccine and compare them to other well-characterized viral vaccine immune responses. Methods: Microarray analyses were performed on human peripheral blood mononuclear cells (PBMCs) to determine changes in transcriptional activity that correlated with changes detected by cellular phenotyping, cytokine signaling, and serological assays. Transcriptional profiles after tularemia vaccination were compared with yellow fever [YF-17D], inactivated [TIV], and live attenuated [LAIV] influenza. Results: Tularemia vaccine lots produced strong innate immune responses by Day 2 after vaccination, with an increase in monocytes, NK cells, and cytokine signaling. T cell responses peaked at Day 14. Changes in gene expression, including upregulation of STAT1, GBP1, and IFIT2, predicted tularemia-specific antibody responses. Changes in CCL20 expression positively correlated with peak CD8+ T cell responses, but negatively correlated with peak CD4+ T cell activation. Tularemia vaccines elicited gene expression signatures similar to other replicating vaccines, inducing early upregulation of interferon-inducible genes. Conclusions: A systems vaccinology approach identified that tularemia vaccines induce a strong innate immune response early after vaccination, similar to the response seen after well-studied viral vaccines, and produce unique transcriptional signatures that are strongly correlated to the induction of T cell and antibody responses.

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

Journal of Virology ◽

10.1128/jvi.01701-16 ◽

2016 ◽

Vol 90 (23) ◽

pp. 10459-10471 ◽

Cited By ~ 13

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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