The Koala Immune Response to Chlamydial Infection and Vaccine Development—Advancing Our Immunological Understanding

Chlamydia is a significant pathogen for many species, including the much-loved Australian marsupial, the koala (Phascolarctos cinereus). To combat this situation, focused research has gone into the development and refinement of a chlamydial vaccine for koalas. The foundation of this process has involved characterising the immune response of koalas to both natural chlamydial infection as well as vaccination. From parallels in human and mouse research, it is well-established that an effective anti-chlamydial response will involve a balance of cell-mediated Th1 responses involving interferon-gamma (IFN-γ), humoral Th2 responses involving systemic IgG and mucosal IgA, and inflammatory Th17 responses involving interleukin 17 (IL-17) and neutrophils. Characterisation of koalas with chlamydial disease has shown increased expression within all three of these major immunological pathways and monitoring of koalas’ post-vaccination has detected further enhancements to these key pathways. These findings offer optimism that a chlamydial vaccine for wider distribution to koalas is not far off. Recent advances in marsupial genetic knowledge and general nucleic acid assay technology have moved koala immunological research a step closer to other mammalian research systems. However, koala-specific reagents to directly assay cytokine levels and cell-surface markers are still needed to progress our understanding of koala immunology.

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Identification of A Novel Picorna-Like Virus, Burpengary Virus, that is Negatively Associated with Chlamydial Disease in the Koala

Viruses ◽

10.3390/v11030211 ◽

2019 ◽

Vol 11 (3) ◽

pp. 211 ◽

Cited By ~ 3

Author(s):

Erin Harvey ◽

Danielle Madden ◽

Adam Polkinghorne ◽

Edward Holmes

Keyword(s):

Immune Response ◽

Infectious Diseases ◽

Complete Genome Sequence ◽

Complete Genome ◽

Chlamydial Infection ◽

Inverse Relationship ◽

Virus Discovery ◽

Data Set ◽

Phascolarctos Cinereus ◽

Chlamydia Pecorum

Koalas (Phascolarctos cinereus) are native Australian marsupials whose populations are in decline from a range of threats. Infectious diseases caused by the bacterium Chlamydia pecorum and other pathogens are of particular concern. We analysed 26 poly-A selected RNA-sequencing libraries from a data set designed to study the immune response of koalas to ocular chlamydial infection. Using virus discovery techniques, we identified the coding-complete genome sequence of a novel picorna-like virus, denoted Burpengary virus, that was most common in south-east Queensland. Notably, abundance measurements of the virus across all 26 libraries revealed an inverse relationship between abundance and ocular disease in koalas, suggesting that the co-infection of Burpengary virus and Chlamydia pecorum is inhibited.

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Comparative magnitude and persistence of SARS-CoV-2 vaccination responses on a population level in Germany

10.1101/2021.12.01.21266960 ◽

2021 ◽

Author(s):

Alex Dulovic ◽

Barbora Kessel ◽

Manuela Harries ◽

Matthias Becker ◽

Julia Ortmann ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Vaccine Development ◽

Population Level ◽

Population Based ◽

Serum Samples ◽

Post Vaccination ◽

Robust Immune Response ◽

Binding Inhibition ◽

Dosing Regimens

AbstractBackgroundWhile SARS-CoV-2 vaccinations were successful in decreasing COVID-19 caseloads, recent increases in SARS-CoV-2 infections have led to questions about duration and quality of the subsequent immune response. While numerous studies have been published on immune responses triggered by vaccination, these often focused on the initial peak response generated in specific population subgroups (e.g. healthcare workers or immunocompromised individuals) and have often only examined the effects of one or two different immunisation schemes.Methods and FindingsWe analysed serum samples from participants of a large German seroprevalence study (MuSPAD) who had received all available vaccines and dose schedules (mRNA-1273, BNT162b2, AZD1222, Ad26.CoV2S.2 or a combination of AZD1222 plus either mRNA-1273 or BNT162b2). Antibody titers against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and the Alpha, Beta, Gamma and Delta variants of concern were analysed using a previously published multiplex immunoassay MULTICOV-AB and an ACE2-RBD competition assay. Among the different vaccines and their dosing regimens, homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was significantly reduced, even compared to AZD1222, with 91.67% of samples being considered non-responsive forACE2 binding inhibition. mRNA-based vaccination induced a higher ratio of RBD- and S1-targeting antibodies than vector-based vaccination, which resulted in an increased proportion of S2-targeting antibodies. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received. When examining antibody kinetics post-vaccination after homologous immunisation regimens, both titers and ACE2 binding inhibition peaked approximately 28 days post-vaccination and then decreased as time increased.ConclusionsAs one of the first and largest population-based studies to examine vaccine responses for all currently available immunisation schemes in Germany, we found that homologous mRNA or heterologous vaccination elicited the highest immune responses. The high percentage of non-responders for Ad26.CoV2.S requires further investigation and suggests that a booster dose with an mRNA-based vaccine may be necessary. The high responses seen in recovered and vaccinated individuals could aid future dose allocation, should shortages arise for certain manufacturers. Given the role of RBD- and S1-specific antibodies in neutralising SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why mRNA vaccines have an increased efficacy compared to vector-based formulations. Further investigation on these differences will be of particular interest for vaccine development and efficacy, especially for the next-generation of vector-based vaccines.

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Identification of a Novel Picorna-Like Virus, Burpengary Virus, That Is Negatively Associated with Chlamydial Disease in the Koala

10.20944/preprints201902.0140.v1 ◽

2019 ◽

Author(s):

Erin Harvey ◽

Danielle Madden ◽

Adam Polkinghorne ◽

Edward C. Holmes

Keyword(s):

Immune Response ◽

Infectious Diseases ◽

Complete Genome Sequence ◽

Complete Genome ◽

Chlamydial Infection ◽

Inverse Relationship ◽

Virus Discovery ◽

Data Set ◽

Phascolarctos Cinereus ◽

Chlamydia Pecorum

Koalas (Phascolarctos cinereus) are native Australian marsupials whose populations are in decline from a range of threats. Infectious diseases caused by the bacterium Chlamydia pecorum and other pathogens are of particular concern. We analysed 26 poly-A selected RNA-sequencing libraries from a data set designed to study the immune response of koalas to ocular chlamydial infection. Using virus discovery techniques, we identified the coding-complete genome sequence of a novel picorna-like virus, denoted Burpengary virus, that was most common in south-east Queensland. Notably, abundance measurements of the virus across all 26 libraries revealed an inverse relationship in prevalence with ocular disease in Koalas, suggesting that co-infection between Burpengary virus and Chlamydia pecorum is inhibited.

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HIV-1 Accessory Proteins: Which one is Potentially Effective in Diagnosis and Vaccine Development?

Protein and Peptide Letters ◽

10.2174/0929866528999201231213610 ◽

2020 ◽

Vol 28 ◽

Author(s):

Alireza Milani ◽

Kazem Baesi ◽

Elnaz Agi ◽

Ghazal Marouf ◽

Maryam Ahmadi ◽

...

Keyword(s):

Immune Response ◽

Vaccine Development ◽

Treated Group ◽

Vaccine Antigen ◽

Accessory Proteins ◽

Serological Method ◽

Th2 Immune Response ◽

Untreated Individuals ◽

Immunogenic Properties ◽

Hiv 1

Background:: The combination antiretroviral therapy (cART) could increase the number of circulating naive CD4 T lymphocytes, but was not able to eradicate human immunodeficiency virus-1 (HIV-1) infection. Objective:: Thus, induction of strong immune responses is important for control of HIV-1 infection. Furthermore, a simple and perfect serological method is required to detect virus in untreated-, treated- and drug resistant- HIV-1 infected individuals. Methods:: This study was conducted to assess and compare immunogenic properties of Nef, Vif, Vpr and Vpu accessory proteins as an antigen candidate in mice and their diagnostic importance in human as a biomarker. Results:: Our data showed that in mice, all heterologous prime/ boost regimens were more potent than homologous prime/ boost regimens in eliciting Th1 response and Granzyme B secretion as CTL activity. Moreover, the Nef, Vpu and Vif proteins could significantly increase Th1 immune response. In contrast, the Vpr protein could considerably induce Th2 immune response. On the other hand, among four accessory proteins, HIV-1 Vpu could significantly detect treated group from untreated group as a possible biomarker in human. Conclusion:: Generally, among accessory proteins, Nef, Vpu and Vif antigens were potentially more suitable vaccine antigen candidates than Vpr antigen. Human antibodies against all these proteins were higher in HIV-1 different groups than healthy group. Among them, Vpu was known as a potent antigen in diagnosis of treated from untreated individuals. The potency of accessory proteins as an antigen candidate in an animal model and a human cohort study are underway.

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The Analysis of Live-Attenuated Piscirickettsia salmonis Vaccine Reveals the Short-Term Upregulation of Innate and Adaptive Immune Genes in Atlantic Salmon (Salmo salar): An In Situ Open-Sea Cages Study

Microorganisms ◽

10.3390/microorganisms9040703 ◽

2021 ◽

Vol 9 (4) ◽

pp. 703

Author(s):

Deborah Vargas ◽

Eva Vallejos-Vidal ◽

Sebastián Reyes-Cerpa ◽

Aarón Oyarzún-Arrau ◽

Claudio Acuña-Castillo ◽

...

Keyword(s):

Immune Response ◽

Atlantic Salmon ◽

Salmo Salar ◽

Cellular Response ◽

Short Term ◽

Live Attenuated Vaccine ◽

Gene Markers ◽

Post Vaccination ◽

Atlantic Salmon Salmo Salar ◽

Piscirickettsia Salmonis

Piscirickettsia salmonis, the etiological agent of the Salmon Rickettsial Septicemia (SRS), is one the most serious health problems for the Chilean salmon industry. Typical antimicrobial strategies used against P. salmonis include antibiotics and vaccines, but these applications have largely failed. A few years ago, the first attenuated-live vaccine against SRS (ALPHA JECT LiVac® SRS vaccine) was released to the market. However, there is no data about the agents involved in the activation of the immune response induced under field conditions. Therefore, in this study we evaluated the expression profile of a set of gene markers related to innate and adaptive immunity in the context of a cellular response in Atlantic salmon (Salmo salar) reared under productive farm conditions and immunized with a live-attenuated vaccine against P. salmonis. We analyzed the expression at zero, 5-, 15- and 45-days post-vaccination (dpv). Our results reveal that the administration of the attenuated live SRS LiVac vaccine induces a short-term upregulation of the cellular-mediated immune response at 5 dpv modulated by the upregulation of ifnα, ifnγ, and the cd4 and cd8α T cell surface markers. In addition, we also registered the upregulation of il-10 and tgfβ. Altogether, the results suggest that a balanced activation of the immune response took place only at early times post-vaccination (5 dpv). The scope of this short-term upregulation of the cellular-mediated immune response against a natural outbreak in fish subjected to productive farm conditions deserves further research.

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Randomized, Blinded, Dose-Ranging Trial of an Ebola Virus Glycoprotein Nanoparticle Vaccine With Matrix-M Adjuvant in Healthy Adults

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz518 ◽

2019 ◽

Vol 222 (4) ◽

pp. 572-582 ◽

Cited By ~ 6

Author(s):

Louis Fries ◽

Iksung Cho ◽

Verena Krähling ◽

Sarah K Fehling ◽

Thomas Strecker ◽

...

Keyword(s):

Public Health ◽

Immune Response ◽

Ebola Virus ◽

Vaccine Development ◽

Phase 1 ◽

Healthy Adults ◽

Wild Type ◽

Dose Ranging ◽

Further Development ◽

Human Vaccine

Abstract Background Ebola virus (EBOV) epidemics pose a major public health risk. There currently is no licensed human vaccine against EBOV. The safety and immunogenicity of a recombinant EBOV glycoprotein (GP) nanoparticle vaccine formulated with or without Matrix-M adjuvant were evaluated to support vaccine development. Methods A phase 1, placebo-controlled, dose-escalation trial was conducted in 230 healthy adults to evaluate 4 EBOV GP antigen doses as single- or 2-dose regimens with or without adjuvant. Safety and immunogenicity were assessed through 1-year postdosing. Results All EBOV GP vaccine formulations were well tolerated. Receipt of 2 doses of EBOV GP with adjuvant showed a rapid increase in anti-EBOV GP immunoglobulin G titers with peak titers observed on Day 35 representing 498- to 754-fold increases from baseline; no evidence of an antigen dose response was observed. Serum EBOV-neutralizing and binding antibodies using wild-type Zaire EBOV (ZEBOV) or pseudovirion assays were 3- to 9-fold higher among recipients of 2-dose EBOV GP with adjuvant, compared with placebo on Day 35, which persisted through 1 year. Conclusions Ebola virus GP vaccine with Matrix-M adjuvant is well tolerated and elicits a robust and persistent immune response. These data suggest that further development of this candidate vaccine for prevention of EBOV disease is warranted.

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Acetylcholine-producing T cells augment innate immune-driven colitis but are redundant in T cell-driven colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00067.2019 ◽

2019 ◽

Vol 317 (5) ◽

pp. G557-G568 ◽

Cited By ~ 2

Author(s):

Rose A. Willemze ◽

David J. Brinkman ◽

Olaf Welting ◽

Patricia H. P. van Hamersveld ◽

Caroline Verseijden ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Inflammatory Cytokine ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Innate Immune ◽

Cytokine Levels ◽

Colitis Model

Clinical trials suggest that vagus nerve stimulation presents an alternative approach to classical immune suppression in Crohn's disease. T cells capable of producing acetylcholine (ChAT+ T cells) in the spleen are essential mediators of the anti-inflammatory effect of vagus nerve stimulation. Besides the spleen, ChAT+ T cells are found abundantly in Peyer’s patches of the small intestine. However, the role of ChAT+ T cells in colitis pathogenesis is unknown. Here, we made use of CD4creChATfl/fl mice (CD4ChAT−/− mice) lacking ChAT expression specifically in CD4+ T cells. Littermates (ChATfl/fl mice) served as controls. In acute dextran sulfate sodium (DSS)-induced colitis (7 days of 2% DSS in drinking water), CD4ChAT−/− mice showed attenuated colitis and lower intestinal inflammatory cytokine levels compared with ChATfl/fl mice. In contrast, in a resolution model of DSS-induced colitis (5 days of 2% DSS followed by 7 days without DSS), CD4ChAT−/− mice demonstrated a worsened colitis recovery and augmented colonic histological inflammation scores and inflammatory cytokine levels as compared with ChATfl/fl mice. In a transfer colitis model using CD4+CD45RBhigh T cells, T cells from CD4ChAT−/− mice induced a similar level of colitis compared with ChATfl/fl T cells. Together, our results indicate that ChAT+ T cells aggravate the acute innate immune response upon mucosal barrier disruption in an acute DSS-induced colitis model, whereas they are supporting the later resolution process of this innate immune-driven colitis. Surprisingly, ChAT expression in T cells seems redundant in the context of T cell-driven colitis. NEW & NOTEWORTHY By using different mouse models of experimental colitis, we provide evidence that in dextran sulfate sodium-induced colitis, ChAT+ T cells capable of producing acetylcholine worsen the acute immune response, whereas they support the later healing phase of this innate immune-driven colitis.

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