Intranasal Vaccination With Multiple Virulence Factors Promotes Mucosal Clearance of Streptococcus suis Across Serotypes and Protects Against Meningitis in Mice

2019 ◽  
Vol 220 (10) ◽  
pp. 1679-1687 ◽  
Author(s):  
Xinxin Xing ◽  
Shuai Bi ◽  
Xin Fan ◽  
Meilin Jin ◽  
Wenjun Liu ◽  
...  

Abstract Background Streptococcus suis is an emerging zoonotic agent. Its natural habitat is the tonsils, which are the main portals of S. suis entry into the bloodstream of pigs. The remarkable variability of the bacteria and complex pathogenic mechanisms make the development of a vaccine a difficult task. Method Five conserved virulence factors involved in critical events of S. suis pathogenesis were combined and used as an intranasal vaccine (V5). The effect of V5 was investigated with intranasal and systemic challenge models. Results V5 induced antibody and T-cell responses at the mucosal site and systemically. The immunity promoted clearance of S. suis from the nasopharynx independent of S. suis serotypes and reduced lethality after systemic challenge with S. suis serotype 2. Moreover, mice that survived sepsis from intravenous infection developed meningitis, whereas none of these mice showed neuropathological symptoms after V5 receipt. Conclusion Intranasal immunization with multiple conserved virulence factors decreases S. suis colonization at the nasopharynx across serotypes and inhibits the dissemination of the bacteria in the host. The protective mucosal immunity effects would potentially reduce the S. suis reservoir and prevent S. suis disease in pigs.

2021 ◽  
Author(s):  
Hiroshi Ishii ◽  
Takushi Nomura ◽  
Hiroyuki Yamamoto ◽  
Masako Nishizawa ◽  
Trang Thi Thu Hau ◽  
...  

Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2480
Author(s):  
Chadaporn Chaiden ◽  
Janthima Jaresitthikunchai ◽  
Narumon Phaonakrop ◽  
Sittiruk Roytrakul ◽  
Anusak Kerdsin ◽  
...  

Streptococcus suis (S. suis) is a zoonotic pathogen causing severe streptococcal disease worldwide. S. suis infections in pigs and humans are frequently associated with the virulent S. suis serotype 2 (SS2). Though various virulence factors of S. suis have been proposed, most of them were not essentially accounted for in the experimental infections. In the present study, we compared the peptidomes of highly virulent SS2 and SS14 in humans, the swine causative serotypes SS7 and SS9, and the rarely reported serotypes SS25 and SS27, and they were cultured in a specified culture medium containing whole blood to simulate their natural host environment. LC-MS/MS could identify 22 unique peptides expressed in the six S. suis serotypes. Under the host-simulated environment, peptides from the ABC-type phosphate transport system (SSU05_1106) and 30S ribosomal protein S2 (rpsB) were detected in the peptidome of virulent SS2 and SS14. Therefore, we suggest that these two proteins or their derived peptides might be involved in the survival of S. suis when simulated with a blood environment.


2019 ◽  
Vol 236 ◽  
pp. 108375 ◽  
Author(s):  
Hanze Liu ◽  
Hao Fu ◽  
Xiaowu Jiang ◽  
Xiayi Liao ◽  
Min Yue ◽  
...  

2009 ◽  
Vol 83 (15) ◽  
pp. 7619-7628 ◽  
Author(s):  
Amy Sexton ◽  
Robert De Rose ◽  
Jeanette C. Reece ◽  
Sheilajen Alcantara ◽  
Liyen Loh ◽  
...  

ABSTRACT There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker β7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sean A. Nelson ◽  
Andrea J. Sant

Yearly administration of influenza vaccines is our best available tool for controlling influenza virus spread. However, both practical and immunological factors sometimes result in sub-optimal vaccine efficacy. The call for improved, or even universal, influenza vaccines within the field has led to development of pre-clinical and clinical vaccine candidates that aim to address limitations of current influenza vaccine approaches. Here, we consider the route of immunization as a critical factor in eliciting tissue resident memory (Trm) populations that are not a target of current licensed intramuscular vaccines. Intranasal vaccination has the potential to boost tissue resident B and T cell populations that reside within specific niches of the upper and lower respiratory tract. Within these niches, Trm cells are poised to respond rapidly to pathogen re-encounter by nature of their anatomic localization and their ability to rapidly deliver anti-pathogen effector functions. Unique features of mucosal immunity in the upper and lower respiratory tracts suggest that antigen localized to these regions is required for the elicitation of protective B and T cell immunity at these sites and will need to be considered as an important attribute of a rationally designed intranasal vaccine. Finally, we discuss outstanding questions and areas of future inquiry in the field of lung mucosal immunity.


2020 ◽  
Vol 5 (52) ◽  
pp. eabb5439
Author(s):  
James G. Bedford ◽  
Melanie Heinlein ◽  
Alexandra L. Garnham ◽  
Thi H. O. Nguyen ◽  
Tom Loudovaris ◽  
...  

The nasal-associated lymphoid tissues (NALTs) are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage. NALTs represent a known site for the deposition of inhaled antigens, but little is known of the mechanisms involved in the induction of immunity within this lymphoid tissue. We find that during the steady state, conventional dendritic cells (cDCs) within the NALTs suppress T cell responses. These cDCs, which are also prevalent within human NALTs (tonsils/adenoids), express a unique transcriptional profile and inhibit T cell proliferation via contact-independent mechanisms that can be diminished by blocking the actions of reactive oxygen species and prostaglandin E2. Although the prevention of unrestrained immune activation to inhaled antigens appears to be the default function of NALT cDCs, inflammation after localized virus infection recruited monocyte-derived DCs (moDCs) to this region, which diluted out the suppressive DC pool, and permitted local T cell priming. Accommodating for inflammation-induced temporal changes in NALT DC composition and function, we developed an intranasal vaccine delivery system that coupled the recruitment of moDCs with the sustained release of antigen into the NALTs, and we were able to substantially improve T cell responses after intranasal immunization. Thus, homeostasis and immunity to inhaled antigens is tuned by inflammatory signals that regulate the balance between conventional and moDC populations within the NALTs.


PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0181920 ◽  
Author(s):  
Jean-Philippe Auger ◽  
Sarah Chuzeville ◽  
David Roy ◽  
Annabelle Mathieu-Denoncourt ◽  
Jianguo Xu ◽  
...  

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