Apoptosis of antigen-specific CTLs contributes to low immune response in gut-associated lymphoid tissue post vaccination

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

Animals ◽

10.3390/ani11020380 ◽

2021 ◽

Vol 11 (2) ◽

pp. 380

Author(s):

Bonnie L Quigley ◽

Peter Timms

Keyword(s):

Immune Response ◽

Chlamydial Infection ◽

Vaccine Development ◽

Interleukin 17 ◽

Phascolarctos Cinereus ◽

Post Vaccination ◽

Research Systems ◽

Cytokine Levels ◽

Nucleic Acid Assay ◽

Immunological Research

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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Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda

Wellcome Open Research ◽

10.12688/wellcomeopenres.15579.1 ◽

2019 ◽

Vol 4 ◽

pp. 182 ◽

Cited By ~ 2

Author(s):

Derick Kimathi ◽

Aitana Juan ◽

Philip Bejon ◽

Rebecca F. Grais ◽

George M. Warimwe ◽

...

Keyword(s):

Immune Response ◽

Randomized Controlled Trials ◽

Yellow Fever ◽

Vaccine Dose ◽

World Health ◽

Yellow Fever Vaccine ◽

Controlled Trials ◽

Post Vaccination ◽

Randomized Controlled ◽

Link Type

Introduction: Yellow fever is endemic in specific regions of sub-Saharan Africa and the Americas, with recent epidemics occurring on both continents. The yellow fever vaccine is effective, affordable and safe, providing life-long immunity following a single dose vaccination. However, the vaccine production process is slow and cannot be readily scaled up during epidemics. This has led the World Health Organization (WHO) to recommend the use of fractional doses as a dose-sparing strategy during epidemics, but there are no randomized controlled trials of fractional yellow fever vaccine doses in Africa. Methods and analysis: We will recruit healthy adult volunteers, adults living with HIV, and children to a series of randomized controlled trials aiming to determine the immunogenicity and safety of fractional vaccine doses in comparison to the standard vaccine dose. The trials will be conducted across two sites; Kilifi, Kenya and Mbarara, Uganda. Recruited participants will be randomized to receive fractional or standard doses of yellow fever vaccine. Scheduled visits will include blood collection for serum and peripheral blood mononuclear cells (PBMCs) before vaccination and on various days – up to 2 years – post-vaccination. The primary outcome is the rate of seroconversion as measured by the plaque reduction neutralization test (PRNT50) at 28 days post-vaccination. Secondary outcomes include antibody titre changes, longevity of the immune response, safety assessment using clinical data, the nature and magnitude of the cellular immune response and post-vaccination control of viremia by vaccine dose. Ethics and dissemination: The clinical trial protocols have received approval from the relevant institutional ethics and regulatory review committees in Kenya and Uganda, and the WHO Ethics Review Committee. The research findings will be disseminated through open-access publications and presented at relevant conferences and workshops. Registration: ClinicalTrials.gov NCT02991495 (registered on 13 December 2016) and NCT04059471 (registered on 15 August 2019).

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COVID19 vaccine type and humoral immune response in patients receiving dialysis

10.1101/2021.08.02.21261516 ◽

2021 ◽

Author(s):

Pablo Garcia ◽

Shuchi Anand ◽

Jialin Han ◽

Maria Montez-Rath ◽

Sumi Sun ◽

...

Keyword(s):

Immune Response ◽

Antibody Index ◽

Igg Antibody ◽

Post Vaccination ◽

Humoral Immune ◽

Vaccination Response ◽

Vaccine Type ◽

Igg Index ◽

Impaired Immune Response ◽

Index Value

Background Patients on dialysis vaccinated with the attenuated adenovirus SARS-CoV-2 vaccine might mount an impaired response to vaccination. Methods We evaluated the humoral vaccination response among 2,099 fully vaccinated patients receiving dialysis. We used commercially available assays (Siemens) to assess prevalence of no response or diminished response to COVID-19 vaccination by vaccine type. We defined no seroconversion as lack of change from negative to positive in total RBD Ig antibody, no detectable response on semiquantitative RBD IgG antibody (index value <1) as no RBD IgG response, and a semiquantitative RBD IgG index value <10 as diminished RBD IgG response Results Of the 2,099 fully vaccinated patients on dialysis, the proportion receiving the mRNA1273, BNT162b2, and Ad26.COV2.S were 62% (n=1316), 20% (n=416) and 18% (n=367), respectively. A third (33.3%) of patients receiving the attenuated adenovirus Ad26.COV2.S vaccine failed to seroconvert and an additional 36% had no detectable or diminished IgG response even 28-60 days post vaccination. Conclusions One in three fully vaccinated patients receiving dialysis had evidence of an impaired immune response to the attenuated adenovirus Ad26.COV2.S vaccine.

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Evaluation of Anti-HBs Antibody Immune Response against Hepatitis B virus in Vaccinated People in а North-eastern Bulgaria Region

Folia Medica ◽

10.3897/folmed.61.e47760 ◽

2019 ◽

Vol 61 (4) ◽

pp. 572-578

Author(s):

Denitsa T. Tsaneva-Damyanova ◽

Liliya I. Ivanova ◽

Silviya N. Pavlova ◽

Svetlana B. Todorova ◽

Tsvetelina K. Popova

Keyword(s):

Immune Response ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Age Groups ◽

University Hospital ◽

Human Pathogens ◽

Serum Samples ◽

Post Vaccination ◽

B Virus ◽

Mass Immunization

Introduction: Hepatitis B virus (HBV) is one of the most significant human pathogens responsible for a huge number of acute and chronic liver infectious diseases worldwide. Aim: To find the duration of post-vaccination immune response in individuals allocated to five age groups from 6 months to 20 years. Materials and methods: All tested subjects were born between 1999 and 2018 and therefore covered by the compulsory vaccination program against hepatitis B. For the serological marker anti-HBs Ab we investigated 449 serum samples taken from ambulatory people and patients of St Marina University Hospital in Varna. Results: A positive antibody response (anti-HBs Ab > 10 mIU/ml) was reported in 79.7% (n = 51) of the group of subjects up to one year old, in 70.0% (n = 196) of the subjects in the age range 1 year/1 month to 15 years, and in 39.3% (n = 33) of the subjects 15 years/1 month to 20 years old. Female sex had a better post-vaccination response than male sex with statistically significant relationship between sex and anti-HBs Ab titer (χ2 = 24.76, p <0.01). Conclusions: Regardless of the mass immunization against HBV in Bulgaria, the relative share of chronic HBV infections does not show a downward trend. Therefore, it is very important to study the duration of the post-vaccination immune response by demonstrating the anti-HBs antibodies and to apply a booster dose from the vaccine if needed.

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Dietary Plasma Proteins Modulate the Immune Response of Diffuse Gut-Associated Lymphoid Tissue in Rats Challenged with Staphylococcus aureus Enterotoxin B

Journal of Nutrition ◽

10.1093/jn/138.3.533 ◽

2008 ◽

Vol 138 (3) ◽

pp. 533-537 ◽

Cited By ~ 41

Author(s):

Anna Pérez-Bosque ◽

Lluïsa Miró ◽

Javier Polo ◽

Louis Russell ◽

Joy Campbell ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Immune Response ◽

Lymphoid Tissue ◽

Plasma Proteins ◽

Enterotoxin B ◽

Staphylococcus Aureus Enterotoxin B

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LB14. Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine Administered by Intramuscular Route in Subjects Aged 65 Years and Older

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy229.2188 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S764-S764 ◽

Cited By ~ 1

Author(s):

Lee-Jah Chang ◽

Ya Meng ◽

Helene Janosczyk ◽

Victoria Landolfi ◽

H Keipp Talbot ◽

...

Keyword(s):

United States ◽

Immune Response ◽

Influenza Vaccine ◽

Standard Dose ◽

The United States ◽

Influenza Vaccines ◽

High Dose ◽

Post Vaccination ◽

B Lineage ◽

Research Grant

Abstract Background Older adults (≥65 years of age) remain at increased risk of influenza because they do not respond to standard dose influenza vaccines as well as younger adults. A high dose, inactivated trivalent influenza vaccine, IIV3-HD, containing four times the antigen content (60 µg hemagglutinin per influenza strain) of standard-dose influenza vaccines has been available in the United States since 2010. Two distinct B influenza lineages (Victoria and Yamagata) have co-circulated for over a decade, making it difficult to predict which will predominate the next season. IIV4-HD has been developed to address the frequent influenza B strain mismatches by incorporating a strain from each B lineage. This pivotal Phase III study evaluated the safety and immunogenicity of IIV4-HD as compared with two IIV3-HD vaccines. Method A randomized, modified double-blind, multicenter study (NCT03282240) was conducted in 2670 healthy subjects in the United States, who were randomly assigned to receive IIV4-HD, a licensed IIV3-HD, or an IIV3-HD with the alternate B influenza strain. Using the hemagglutinin inhibition (HAI) assay at baseline and 28 days after vaccination, post-vaccination geometric mean titers and seroconversion rates were measured. Safety data were collected through 6 months post-vaccination. Result IIV4-HD was noninferior to the licensed IIV3-HD and the investigational IIV3-HD (containing the alternate B strain) for all four influenza strains as assessed by HAI GMTs and seroconversion rates. Moreover, IIV4-HD induced a superior immune response (HAI GMTs and seroconversion rates) compared with the immune response induced by the IIV3-HD that does not contain the corresponding B strain. Reactogenicity profiles were comparable across all study groups. Most unsolicited adverse events were of Grade 1 or Grade 2 intensity. One serious adverse event considered related by the Investigator was reported in the IIV4-HD group. Conclusion Vaccination of adults 65 years of age and older with IIV4-HD was found to be noninferior to two IIV3-HD vaccines with a similar safety profile. The addition of a second B lineage strain does not adversely affect the safety or immunogenicity profile of IIV4-HD compared with IIV3-HD. Disclosures L. J. Chang, Sanofi Pasteur: Employee, Salary. Y. Meng, Sanofi Pasteur: Employee, Salary. H. Janosczyk, Sanofi Pasteur: Employee, Salary. V. Landolfi, Sanofi Pasteur: Employee, Salary. H. K. Talbot, Sanofi Pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

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Local Expression of Secondary Lymphoid Tissue Chemokine Delivered by Adeno-Associated Virus within the Tumor Bed Stimulates Strong Anti-Liver Tumor Immunity

Journal of Virology ◽

10.1128/jvi.00208-07 ◽

2007 ◽

Vol 81 (17) ◽

pp. 9502-9511 ◽

Cited By ~ 27

Author(s):

Chun-min Liang ◽

Cui-ping Zhong ◽

Rui-xia Sun ◽

Bin-bin Liu ◽

Cheng Huang ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Lymphoid Tissue ◽

Critical Role ◽

Antitumor Immune Response ◽

Target Cells ◽

Lymphoid Tissues ◽

Adeno Associated Virus ◽

Secondary Lymphoid Tissue ◽

Local Expression

ABSTRACT Development of an effective antitumor immune response depends on the appropriate interaction of effector and target cells. Thus, the expression of chemokines within the tumor may induce a more potent antitumor immune response. Secondary lymphoid tissue chemokine (SLC) is known to play a critical role in establishing a functional microenvironment in secondary lymphoid tissues. Its capacity to attract dendritic cells (DCs) and colocalize them with T cells makes it a good therapeutic candidate against cancer. In this study, we used SLC as a treatment for tumors established from a murine hepatocellular carcinoma model. SLC was encoded by recombinant adeno-associated virus (rAAV), a system chosen for the low host immunity and high efficiency of transduction, enabling long-term expression of the gene of interest. As a result, rAAV-SLC induced a significant delay of tumor progression, which was paralleled by a profound infiltration of DCs and activated CD4+ T cells and CD8+ T cells (CD3+ CD69+ cells) into the tumor site. In addition, rAAV-SLC treatment was also found to reduce tumor growth in nude mice, most likely due to inhibition of neoangiogenesis. In conclusion, local expression of SLC by rAAV represents a promising approach to induce immune-mediated regression of malignant tumors.

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SAT-452 Dysregulation of immune response in Nasal-associated lymphoid tissue in murine IgA nephropathy

Kidney International Reports ◽

10.1016/j.ekir.2020.02.480 ◽

2020 ◽

Vol 5 (3) ◽

pp. S189

Author(s):

T. Kano ◽

H. Suzuki ◽

M. Yuko ◽

Y. Nihei ◽

F. Yusuke ◽

...

Keyword(s):

Immune Response ◽

Iga Nephropathy ◽

Lymphoid Tissue

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Enhancement of immune response against Bordetella spp. by disrupting immunomodulation

Scientific Reports ◽

10.1038/s41598-019-56652-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Monica C. Gestal ◽

Laura K. Howard ◽

Kalyan Dewan ◽

Hannah M. Johnson ◽

Mariette Barbier ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Immune Cells ◽

Lymphoid Tissue ◽

Protective Immunity ◽

Inflammatory Cells ◽

Host Immune System ◽

Initial Growth ◽

Wild Type ◽

Sterilizing Immunity

AbstractWell-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the respiratory tract of mice, its natural host, but did increase activation of the inflammasome pathway, and recruitment of inflammatory cells. The mutant lacking btrS recruited many more B and T cells into the lungs, where they rapidly formed highly organized and distinctive Bronchial Associated Lymphoid Tissue (BALT) not induced by any wild type Bordetella species, and a much more rapid and strong antibody response than observed with any of these species. Immunity induced by the mutant was measurably more robust in all respiratory organs, providing completely sterilizing immunity that protected against challenge infections for many months. Moreover, the mutant induced sterilizing immunity against infection with other classical bordetellae, including B. pertussis and B. parapertussis, something the current vaccines do not provide. These findings reveal profound immunomodulation by bordetellae and demonstrate that by disrupting it much more robust protective immunity can be generated, providing a pathway to greatly improve vaccines and preventive treatments against these important pathogens.

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