scholarly journals A live attenuated vaccine model confers cross-protective immunity against different species of the Leptospira genus

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elsio A Wunder ◽  
Haritha Adhikarla ◽  
Camila Hamond ◽  
Katharine A Owers ◽  
Li Liang ◽  
...  

Leptospirosis is the leading zoonotic disease in terms of morbidity and mortality worldwide. Effective prevention is urgently needed as the drivers of disease transmission continue to intensify. The key challenge has been developing a widely-applicable vaccine that protects against the >300 serovars that can cause leptospirosis. Live attenuated mutants are enticing vaccine candidates and poorly explored in the field. We evaluated a recently characterized motility-deficient mutant lacking the expression of a flagellar protein, FcpA. Although the fcpA- mutant has lost its ability to cause disease, transient bacteremia was observed. In two animal models, immunization with a single dose of the fcpA- mutant was sufficient to induce a robust anti-protein antibodies response that promoted protection against infection with different pathogenic Leptospira species. Furthermore, characterization of the immune response identified a small repertoire of biologically relevant proteins that are highly conserved among pathogenic Leptospira species and potential correlates of cross-protective immunity.

Author(s):  
Elsio A. Wunder ◽  
Haritha Adhikarla ◽  
Camila Hamond ◽  
Katharine A. Owers ◽  
Li Liang ◽  
...  

ABSTRACTLeptospirosis is the leading zoonotic disease in terms of morbidity and mortality worldwide with a great health and economic impact in both humans and animals. Effective prevention is urgently needed as rapid urbanization, climate change and drivers of disease transmission continue to intensify. The key challenge has been developing a widely-applicable vaccine that protects against the 13 different pathogenic species and >300 serovars that can cause leptospirosis, providing a major public health benefit and opportunity to leverage One Health approaches. Live attenuated mutants that can boost immunity and induce protection are enticing vaccine candidates and poorly explored in the field. We evaluated a recently characterized motility-deficient mutant lacking the expression of a flagellar protein, FcpA. Although the fcpA- mutant has lost its ability to penetrate mucous membranes and cause disease, a transient bacteremia prior to clearance by the host immune response was observed. In two animal models, immunization with a single dose of the fcpA- mutant was sufficient to induce robust anti-protein antibodies response that promoted protection against infection with different Leptospira spp. species. Furthermore, characterization of the immune response identified a small repertoire of biologically relevant proteins that are highly conserved among pathogenic Leptospira species and potential correlates of cross-protective immunity.


2015 ◽  
Vol 73 (6) ◽  
Author(s):  
Araceli E. Santiago ◽  
Barbara J. Mann ◽  
Aiping Qin ◽  
Aimee L. Cunningham ◽  
Leah E. Cole ◽  
...  

COVID ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 608-621
Author(s):  
Arthur W. Currier ◽  
Madeline C. Jeshurin ◽  
Valerie B. Sampson

Coronavirus disease-2019 (COVID-19) vaccines are being used across the globe to reduce the risk of developing COVID-19, stop the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and end the pandemic. To address this, a massive global effort is underway for development of COVID-19 vaccines. As of September 2021, the World Health Organization (WHO) has documented 331 COVID-19 vaccine candidates, and 107 are in clinical evaluation, with 8 in Phase IV and 30 in Phase III clinical trials (WHO; COVID-19 vaccine tracker). At least 13 different vaccines are being issued for emergency use authorization. Specifically, the goal is to produce protective immunity to SARS-CoV-2 infection by stimulating an immune response to either the whole virus, viral protein, or nucleic acid products. The spike (S) proteins of SARS-CoV-2 that give the characteristic “corona” appearance of this family of viruses has emerged as an effective target for vaccines. Other viral candidates that are being developed also aim to produce immunity for COVID-19. In this review, we describe the different vaccine platforms, target candidates for vaccines, and their progress in COVID-19 vaccine development. This is critical since newly discovered SARS-CoV-2 variants of interest require understanding of how vaccines may provide the most effective long-term protection against infection.


2009 ◽  
Vol 90 (8) ◽  
pp. 1962-1966 ◽  
Author(s):  
Inger K. Damon ◽  
Whitni B. Davidson ◽  
Christine M. Hughes ◽  
Victoria A. Olson ◽  
Scott K. Smith ◽  
...  

The search for a ‘third’-generation smallpox vaccine has resulted in the development and characterization of several vaccine candidates. A significant barrier to acceptance is the absence of challenge models showing induction of correlates of protective immunity against variola virus. In this light, virus neutralization provides one of few experimental methods to show specific ‘in vitro’ activity of vaccines against variola virus. Here, we provide characterization of the ability of a modified vaccinia virus Ankara vaccine to induce variola virus-neutralizing antibodies, and we provide comparison with the neutralization elicited by standard Dryvax vaccination.


2019 ◽  
Vol 19 (14) ◽  
pp. 1263-1274 ◽  
Author(s):  
Anuradha Kalani ◽  
Komal Kalani ◽  
Poonam Chaturvedi ◽  
Pankaj Chaturvedi

Background:Filariasis affects millions of people in tropical and subtropical regions of the world and is caused by nematode roundworm. In order to develop a vaccine and specific diagnostic tests, it is important to characterize different stages of the filarial worms. Microfilariae (Mf) stage of the roundworm is found in host’s blood or lymph vessels and can be important not only for developing better immunodiagnostics but also for understanding immune recognition and its relevance to immunepathogenesis and protective immunity.Objective:The present study aimed to immunocharacterize Mf and adult worm antigens that could be helpful in future diagnostic tests.Method:Four different immune sera against Setaria cervi intact live, intact live with adjuvant, intact glutaraldehyde fixed with adjuvant and total somatic Mf were prepared and used for the immunocharacterization of Mf antigens.Results:Our study results suggest that compared to fixed intact Mf, live intact Mf are more immunogenic, as the immune sera generated against intact live Mf showed high ELISA reactivity with Setaria cervi Mf and adult worm antigens. All the four immune sera IgG fractions had surface specificity as determined through considerable ELISA reactivity with S. cervi intact Mf. When tested under native conditions (immunoelectrophoresis and crossed immunoelectrophoresis), all the four immune rabbit sera were able to detect antigens of S. cervi Mf and adult stages.Conclusion:These results can be useful in detailed understanding of the complex nature of the Mf and adult antigens, which are prerequisites in the development of vaccine and more specific diagnostic tests.


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