whole cell vaccine
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Author(s):  
Annieck M Diks ◽  
Pauline Versteegen ◽  
Cristina Teodosio ◽  
Rick J Groenland ◽  
Bas de Mooij ◽  
...  

Pertussis is a vaccine-preventable disease caused by the bacterium Bordetella pertussis. Over the past years, the incidence and mortality of pertussis increased significantly. A possible cause is the switch from whole cell to acellular pertussis vaccines, although other factors may also contribute. To develop future vaccines and improve current vaccination strategies, it is critical to understand factors influencing the generation of immunological memory. We applied high-dimensional flow cytometry to investigate changes in B cells in individuals of different ages and distinct priming backgrounds upon administration of an acellular pertussis booster vaccine. These findings were correlated to vaccine-specific plasma cells and serum Ig levels. Expansion and maturation of plasma cells 7 days post-vaccination was the most prominent cellular change in all age groups, and was most pronounced for more mature IgG1+ plasma cells. Cellular responses were stronger in individuals primed with whole cell vaccine than in individuals primed with acellular vaccine. Moreover, IgG1+ plasma cell expansion weakly correlated with Prn- and PT- specific serum IgG levels. Our study points at plasma cells as a potential early cellular marker of an immune response and contributes to understanding differences in immune responses between age groups and priming backgrounds.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Cuicui Ma ◽  
Xiao Ma ◽  
Boguang Jiang ◽  
Hailong Pan ◽  
Xueyuan Liao ◽  
...  

AbstractPseudomonas aeruginosa infection continues to be a major threat to global public health, and new safe and efficacious vaccines are needed for prevention of infections caused by P. aeruginosa. X-ray irradiation has been used to prepare whole-cell inactivated vaccines against P. aeruginosa infection. However, the immunological mechanisms of X-ray-inactivated vaccines are still unclear and require further investigation. Our previous study found that an X-ray-inactivated whole-cell vaccine could provide protection against P. aeruginosa by boosting T cells. The aim of the present study was to further explore the immunological mechanisms of the vaccine. Herein, P. aeruginosa PAO1, a widely used laboratory strain, was utilized to prepare the vaccine, and we found nucleic acids and 8-hydroxyguanosine in the supernatant of X-ray-inactivated PAO1 (XPa). By detecting CD86, CD80, and MHCII expression, we found that XPa fostered dentritic cell (DC) maturation by detecting. XPa stimulated the cGAS-STING pathway as well as Toll-like receptors in DCs in vitro, and DC finally underwent apoptosis and pyroptosis after XPa stimulation. In addition, DC stimulated by XPa induced CD8+ T-cell proliferation in vitro and generated immunologic memory in vivo. Moreover, XPa vaccination induced both Th1 and Th2 cytokine responses in mice and reduced the level of inflammatory factors during infection. XPa protected mice in pneumonia models from infection with PAO1 or multidrug-resistant clinical isolate W9. Chronic obstructive pulmonary disease (COPD) mice immunized with XPa could resist PAO1 infection. Therefore, a new mechanism of an X-ray-inactivated whole-cell vaccine against P. aeruginosa infection was discovered in this study.


Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1223
Author(s):  
Carrie Mae Long

Q fever is a zoonotic disease caused by the intracellular pathogen Coxiella burnetii. This disease typically manifests as a self-limiting, febrile illness known as acute Q fever. Due to the aerosol transmissibility, environmental persistence, and infectivity of C. burnetii, this pathogen is a notable bioterrorism threat. Despite extensive efforts to develop next-generation human Q fever vaccines, only one vaccine, Q-Vax®, is commercially available. Q-Vax® is a phase I whole-cell vaccine, and its licensed use is limited to Australia, presumably due to the potential for a post-vaccination hypersensitivity response. Pre-clinical Q fever vaccine development is a major area of interest, and diverse approaches have been undertaken to develop an improved Q fever vaccine. Following a brief history of Q fever vaccine development, current approaches will be discussed along with future considerations for an improved Q fever vaccine.


2021 ◽  
Vol 12 ◽  
Author(s):  
Alycia P. Fratzke ◽  
Anthony E. Gregory ◽  
Erin J. van Schaik ◽  
James E. Samuel

Q-VAX®, a whole cell, formalin-inactivated vaccine, is the only vaccine licensed for human use to protect against Coxiella burnetii, the cause of Q fever. Although this vaccine provides long-term protection, local and systemic reactogenic responses are common in previously sensitized individuals which prevents its use outside of Australia. Despite the importance of preventing these adverse reactions to develop widely accepted, novel vaccines against C. burnetii, little is understood about the underlying cellular mechanisms. This is mostly attributed to the use of a guinea pig reactogenicity model where complex cellular analysis is limited. To address this, we compared three different mouse strains develop a model of C. burnetii whole cell vaccine reactogenic responses. SKH1 and C57Bl/6, but not BALBc mice, develop local granulomatous reactions after either infection- or vaccine-induced sensitization. We evaluated local and systemic responses by measuring T cell populations from the vaccination site and spleen during elicitation using flow cytometry. Local reaction sites showed influx of IFNγ+ and IL17a+ CD4 T cells in sensitized mice compared with controls and a reduction in IL4+ CD4 T cells. Additionally, sensitized mice showed a systemic response to elicitation by an increase in IFNγ+ and IL17a+ CD4 T cells in the spleen. These results indicate that local and systemic C. burnetii reactogenic responses are consistent with a Th1 delayed-type hypersensitivity. Our experiments provide insights into the pathophysiology of C. burnetii whole cell vaccine reactogenicity and demonstrate that C57Bl/6 and SKH1 mice can provide a valuable model for evaluating the reactogenicity of novel C. burnetii vaccine candidates.


2021 ◽  
Author(s):  
Nazmun Sharmin ◽  
Mahbub E Khoda ◽  
S. M. Shamsuzzaman ◽  
Mohammad Nazim Uddin

Due to the rapid emergence of extensively drug-resistant (XDR) strains worldwide there is a necessity for greater consideration for the role of preventive vaccines to combat these pathogens. The study reported the effectiveness of a heat-inactivated whole-cell vaccine (HI-WCV) against A. baumannii to produce protective immunity with evaluation of the bactericidal antibody responses in mice after intramuscular inoculation with different XDR strains of A. baumannii Six XDR A. baumannii strains emulsified with complete freund's adjuvant (CFA) were used for intramuscular inoculation in the experimental group of mice (n=4) in three different phases on 14 days interval whereas placebo-controlled mice (n=4) received phosphate-buffered saline emulsified with CFA in same the schedule. Serum was collected from tail blood of each mouse on 10th day after each inoculation and by cardiac puncture on 14th day after lethal dose from the experimental group and after death of the placebo-controlled group. Mice inoculated with heat-inactivated whole-cell vaccine survived and showed a higher neutralizing (IgG) antibody response after 2nd (>7-fold titre) and 3rd inoculation (>12-fold titre) whereas all mice from placebo-controlled group did not survived. Sera from experimental group of mice collected (38th day) after 3rd inoculation resulted in higher serum bactericidal killing index (42.12) after three hours incubation with an XDR A. baumannii over sera collected after 1st and 2nd inoculation (50% cutoff value=14.5). These results suggest that intramuscular vaccination with heat-inactivated whole-cell vaccine stimulated IgG antibody responses that can increase murine survival after XDR A. baumannii infection.


Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 844
Author(s):  
Feng-Jie Su ◽  
Meei-Mei Chen

Lactococcus garvieae (L. garvieae) is an important pathogen that causes enormous economic losses in both marine and freshwater aquaculture. At present, antibiotics are the only option for farmers to reduce the losses caused by L. garvieae. However, the usage of antibiotics leads to environmental pollution and the production of drug-resistant strains of bacteria. Therefore, vaccination is preferred as an alternative method to prevent infectious diseases. In this study, we describe an effective approach to the production of an oral biofilm vaccine, using bacteria grown on chitosan particles to form biofilms, and thus providing an inactive pathogen that enhances the immune response in fish. We observed the formation of a biofilm on chitosan particles and administered the novel oral biofilm vaccine to fish. We analyzed the immune responses, including antibody production, phagocytic ability, albumin/globulin ratio and immune-related genes, of vaccinated and control groups of black mullet. Our results show that the phagocytic ability of the biofilm vaccine group was 84%, which is significantly higher than that of the control group, and the antibody production in this group was significantly higher compared with the other group. The mRNA expression levels of immune-related genes (TLR2, IL-1β, TNF-α) were significantly upregulated in the spleen after vaccination. In challenge experiments, the relative percent survival (RPS) was 77% in the biofilm vaccine group, 18% in the whole-cell vaccine group, and 0% in the chitosan particle group at 32 days post-vaccination. In addition, we also found that the relative percent survival (RPS) at 1 day post-vaccination was 74% in the biofilm vaccine group, 42% in the whole-cell vaccine group, and 26% in the chitosan particle group. In both long-term and short-term challenge experiments, the viability of the biofilm vaccine group was significantly higher than that of the whole-cell, chitosan particle and PBS groups. We conclude that based on its protective effect, the L. garvieae biofilm vaccine is better than the whole-cell vaccine when challenged several weeks after vaccination. In addition, the biofilm vaccine also has a greater protective effect than the whole-cell vaccine when challenged immediately after vaccination. Therefore, the biofilm vaccine might represent a novel method for the prevention and treatment of L. garvieae infection.


Author(s):  
Samaneh Saedi ◽  
Azadeh Safarchi ◽  
Faranak Tayebzadeh Moghadam ◽  
Siamak Heidarzadeh ◽  
Vajihe Sadat Nikbin ◽  
...  

Background: Bordetella pertussis, a highly contagious respiratory. Notably, the resurgence of pertussis has recently been associated with the lacking production of vaccine virulence factors. This study aimed to screen pertactin (Prn) and filamentous hemagglutinin (Fha) production in Iran with 50 years' whole cell vaccine (WCV) immunization program. Methods: Overall, 130 B. pertussis isolates collected from Pertussis Reference Laboratory of Iran during 2005-2018. Real-time PCR was performed by targeting IS481, ptxP, IS1001 and IS1002 for species confirmation of B. pertussis. Western-blot was used to evaluate the expression of virulence factors (pertactin and filamentous hemagglutinin). Results: All tested B. pertussis isolates expressed Prn and all except two isolates expressed Fha. We have sequenced genomes of these strains and identified differences compared with genome reference B. pertussis Tohama I. Conclusion: Many countries reporting Prn and Fha-deficiency due to acellular vaccine (ACV) pressure. Our results demonstrate in a country with WCV history, Fha-deficient isolates may rise independently. However, Prn-deficient isolates are more under the ACV pressure in B. pertussis isolates. Continues surveillance will provide a better understanding of the effect of WCV on the evolution of the pathogen deficiency.  


Vaccine X ◽  
2021 ◽  
pp. 100103
Author(s):  
Daniela Leite ◽  
Carlos Henrique Camargo ◽  
Suely Sanae Kashino ◽  
Ricardo Polatto ◽  
Luciano Moura Martins ◽  
...  

Author(s):  
Niina Ahvenainen ◽  
Timothée Dub ◽  
Aapo Knuutila ◽  
Alex-Mikael Barkoff ◽  
Jussi Sane ◽  
...  

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