Effects of immunostimulators of microbial origin on T cells of pigs vaccinated with attenuated vaccine against Aujeszkyʼs disease

2021 ◽  
pp. 110365
Author(s):  
Miroslav Andrišić ◽  
Irena Žarković ◽  
Ksenija Šandor ◽  
Anja Vujnović ◽  
Eleonora Perak Junaković ◽  
...  
Keyword(s):  
T Cells ◽  
Attenuated Vaccine ◽  
Microbial Origin

scholarly journals T Cell Responses Induced by Attenuated Flavivirus Vaccination Are Specific and Show Limited Cross-Reactivity with Other Flavivirus Species

2020 ◽  
Vol 94 (10) ◽  
Author(s):  
Alba Grifoni ◽  
Hannah Voic ◽  
Sandeep Kumar Dhanda ◽  
Conner K. Kidd ◽  
James D. Brien ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Yellow Fever ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cross Reactivity ◽  
Live Attenuated Vaccine ◽  
Cell Responses ◽  
Attenuated Vaccine ◽  
E Protein

ABSTRACT Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. In this study, we tested pools of epitopes derived from dengue (DENV), Zika (ZIKV), Japanese encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by intracellular cytokine staining (ICS) using peripheral blood mononuclear cells (PBMCs) of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccine. CD8 T cell responses recognized epitopes from multiple flaviviruses; however, the magnitude of cross-reactive responses was consistently severalfold lower than those to the autologous epitope pools and was associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing 29 different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with >100-fold-lower antigen sensitivity for most other flaviviruses, with no cross-recognition of YFV-derived peptides. CD8 and CD4 TCL from YF17D vaccinees were associated with very limited cross-reactivity with any other flaviviruses and in five out of eight cases >1,000-fold-lower antigen sensitivity. Overall, our data suggest limited cross-reactivity for both CD4 and CD8 T cell responses between flaviviruses and have implications for understanding immunity elicited by natural infection and strategies to develop live attenuated vaccines against flaviviral species. IMPORTANCE The envelope (E) protein is the dominant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV). Accordingly, several DENV vaccine constructs use the E protein in a live attenuated vaccine format, utilizing a backbone derived from a heterologous flavivirus (such as YF) as a delivery vector. This backbone comprises the nonstructural (NS) and capsid (C) antigens, which are dominant targets of T cell responses. Here, we demonstrate that cross-reactivity at the level of T cell responses among different flaviviruses is very limited, despite high levels of sequence homology. Thus, the use of heterologous flavivirus species as a live attenuated vaccine vector is not likely to generate optimal T cell responses and might thus impair vaccine performance.

scholarly journals The Feasibility of Using Coxiella burnetii Avirulent Nine Mile Phase II Viable Bacteria as a Live Attenuated Vaccine Against Q fever

2021 ◽  
Vol 12 ◽  
Author(s):  
Venkatesh Kumaresan ◽  
Shawkat Alam ◽  
Yan Zhang ◽  
Guoquan Zhang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Phase Ii ◽  
Protective Immunity ◽  
Q Fever ◽  
Significant Protection ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Deficient Mice

This study aimed to explore if viable C. burnetii avirulent Nine Mile phase II (NMII) can elicit protective immunity against virulent NM phase I (NMI) infection. Interestingly, mice immunized with viable NMII elicited significant protection against NMI infection at different time points post-immunization. Viable NMII induced a dose-dependent NMI-specific IgG response in mice, but all doses of NMII-immunized mice conferred a similar level of protection. Comparing different routes of immunization indicated that intranasally immunized mice showed significantly higher levels of protection than other immunization routes. The observation that viable NMII induced a similar level of long-term protection against NMI challenge as the formalin-inactivated NMI vaccine (PIV) suggests that viable NMII bacteria can induce a similar level of long-term protection against virulent NMI challenge as the PIV. Viable NMII also induced significant protection against challenge with virulent Priscilla and Scurry strains, suggesting that viable NMII can elicit broad protection. Immune sera and splenocytes from viable NMII-immunized mice are protective against NMI infection, but immune serum-receiving mice did not control NMI replication. Additionally, viable NMII conferred a comparable level of protection in wild-type, CD4+ T cell-deficient, and CD8+ T cell-deficient mice, and partial protection in B cell-deficient mice. However, NMII-immunized T cell-deficient mice were unable to prevent C. burnetii replication. Thus, both B cells and T cells are required for viable NMII-induced protective immunity but T cells may play a critical role. Collectively, this study demonstrates the feasibility of using avirulent NMII as a live attenuated vaccine against human Q fever.

scholarly journals Humoral and Cell-Mediated Immune Response Validation in Calves after a Live Attenuated Vaccine of Babesia bigemina

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 936
Author(s):  
Umber Rauf ◽  
Muhammad Suleman ◽  
Asadullah Abid ◽  
Hamna Jamil ◽  
Harish Menghwar ◽  
...  
Keyword(s):  
T Cells ◽  
Economic Losses ◽  
Single Shot ◽  
Babesia Bigemina ◽  
Post Challenge ◽  
Igg Antibody ◽  
Live Attenuated Vaccine ◽  
Cattle Industry ◽  
Attenuated Vaccine ◽  
Cell Mediated Immune Response

The current vaccines to control bovine Babesia bigemina (B. bigemina) infection are not fully protective and vaccination failures incur heavy losses to the cattle industry around the world. Using modified micro-aerophilous stationary phase, we developed a culture-derived attenuated live vaccine against B. bigemina and tested a single subcutaneous inoculation of 2 × 108 infected erythrocytes in calves. The protection was measured after a lethal intravenous challenge with 5 × 108 virulent calf-derived B. bigemina. Our results demonstrated that a single shot of attenuated vaccine was capable of inducing robust humoral and cell-mediated immune responses in calves. We found a significant increase in the IgG antibody titers post-challenge and a strong proliferation of both CD4+ and CD8+ T cells contributing towards the protection. Our vaccine provided complete protection and parasitic clearance, which was followed for more than 100 days post-challenge. This immunity against babesiosis was directly linked to strong humoral responses; however, the parasitic clearance was attributed to significant T cells effector responses in vaccinated calves as compared to the infected control calves. We anticipate that these results will be helpful in the development of more efficient culture-derived vaccines against Babesia infections, thus reducing significant global economic losses to farmers and the cattle industry.

scholarly journals CD8+T Cells Define an Unexpected Role in Live-Attenuated Vaccine Protective Immunity againstChlamydia trachomatisInfection in Macaques

2014 ◽  
Vol 192 (10) ◽  
pp. 4648-4654 ◽  
Author(s):  
Norma Olivares-Zavaleta ◽  
William M. Whitmire ◽  
Laszlo Kari ◽  
Gail L. Sturdevant ◽  
Harlan D. Caldwell
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine

scholarly journals T cell responses induced by attenuated flavivirus vaccination are specific and show limited cross-reactivity with other flavivirus species

2020 ◽  
Author(s):  
Alba Grifoni ◽  
Hannah Voic ◽  
Sandeep Kumar Dhanda ◽  
Conner K. Kidd ◽  
James D Brien ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Yellow Fever ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cross Reactivity ◽  
Live Attenuated Vaccine ◽  
Cell Responses ◽  
Attenuated Vaccine ◽  
E Protein

AbstractMembers of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. Here, we tested pools of epitopes derived from dengue (DENV), zika (ZIKV), Japanese Encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by Intracellular Cytokine Staining (ICS) using PBMCs of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccines. CD8 T cell responses recognized epitopes from multiple flaviviruses, however, the magnitude of cross-reactive responses was consistently several-fold lower than those to the autologous epitope pools, and associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing twenty-nine different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with more than 100-fold lower antigen sensitivity for most other flaviviruses, with no cross-recognition of YFV derived peptides. CD8 and CD4 TCL from YF17D vaccinees were associated with very limited cross-reactivity with any other flaviviruses, and in five out of eight cases more than 1000-fold lower antigen sensitivity. Overall, our data suggest limited cross-reactivity for both CD4 and CD8 T cell responses between flaviviruses and has implications for understanding immunity elicited by natural infection, and strategies to develop live attenuated vaccines against flaviviral species.ImportanceThe envelope (E) protein is the dominant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV). Accordingly, several DENV vaccine constructs use the E protein in a live attenuated vaccine format, utilizing a backbone derived from a heterologous flavivirus (such as YF) as a delivery vector. This backbone comprises the non-structural (NS) and capsid (C) antigens which are dominant targets of T cell responses. Here, we demonstrate that cross-reactivity at the level of T cell responses amongst different flaviviruses is very limited, despite high levels of sequence homology. Thus, the use of heterologous flavivirus species as a live attenuated vaccine vector is not likely to generate optimal T cell responses, and might thus impair vaccine performance.

scholarly journals Mucosal Immunization with the Live Attenuated Vaccine SPY1 Induces Humoral and Th2-Th17-Regulatory T Cell Cellular Immunity and Protects against Pneumococcal Infection

2014 ◽  
Vol 83 (1) ◽  
pp. 90-100 ◽  
Author(s):  
Xiuyu Xu ◽  
Hong Wang ◽  
Yusi Liu ◽  
Yiping Wang ◽  
Lingbing Zeng ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Comprehensive Evaluation ◽  
Critical Role ◽  
Pneumococcal Infection ◽  
Invasive Infection ◽  
Mucosal Immunization ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Pneumococcal Colonization

Mucosal immunization with attenuated vaccine can protect against pneumococcal invasion infection, but the mechanism was unknown. Our study found that mucosal delivery with the live attenuated SPY1 vaccine strain can confer T cell- and B cell-dependent protection against pneumococcal colonization and invasive infection; yet it is still unclear which cell subsets contribute to the protection, and their roles in pneumococcal colonization and invasion remain elusive. Adoptive transfer of anti-SPY1 antibody conferred protection to naive μMT mice, and immune T cells were indispensable to protection examined in nude mice. A critical role of interleukin 17A (IL-17A) in colonization was demonstrated in mice lacking IL-17A, and a vaccine-specific Th2 immune subset was necessary for systemic protection. Of note, we found that SPY1 could stimulate an immunoregulatory response and that SPY1-elicited regulatory T cells participated in protection against colonization and lethal infection. The data presented here aid our understanding of how live attenuated strains are able to function as effective vaccines and may contribute to a more comprehensive evaluation of live vaccines and other mucosal vaccines.

scholarly journals Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδT Cell Intracorneal Infiltration

2021 ◽  
Vol 12 ◽  
Author(s):  
Rafiq Nabi ◽  
Andrew C. Lewin ◽  
Therese M. Collantes ◽  
Vladimir N. Chouljenko ◽  
Konstantin G. Kousoulas
Keyword(s):  
T Cells ◽  
Vaccine Strain ◽  
Neutralizing Antibodies ◽  
Γδ T Cells ◽  
Neutrophil Infiltration ◽  
Developed Countries ◽  
Ocular Infection ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Hsv 1

Herpes simplex virus type-1 (HSV-1) ocular infection is one of the leading causes of infectious blindness in developed countries. The resultant herpetic keratitis (HK) is caused by an exacerbated reaction of the adaptive immune response that persists beyond virus clearance causing substantial damage to the cornea. Intramuscular immunization of mice with the HSV-1(VC2) live-attenuated vaccine strain has been shown to protect mice against lethal ocular challenge. Herein, we show that following ocular challenge, VC2 vaccinated animals control ocular immunopathogenesis in the absence of neutralizing antibodies on ocular surfaces. Ocular protection is associated with enhanced intracorneal infiltration of γδ T cells compared to mock-vaccinated animals. The observed γδ T cellular infiltration was inversely proportional to the infiltration of neutrophils, the latter associated with exacerbated tissue damage. Inhibition of T cell migration into ocular tissues by the S1P receptors agonist FTY720 produced significant ocular disease in vaccinated mice and marked increase in neutrophil infiltration. These results indicate that ocular challenge of mice immunized with the VC2 vaccine induce a unique ocular mucosal response that leads into the infiltration of γδ T cells resulting in the amelioration of infection-associated immunopathogenesis.

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