Serotype 3 Streptococcus pneumoniae Escapes the Immune Responses Induced by PCV13 in Mice With High Susceptibility to Infection.

Background: Streptococcus pneumoniae (pneumococcus) is a common cause of respiratory and invasive infections in humans. PCV13, a pneumococcal conjugate vaccine used globally, is highly effective against diseases caused by pneumococcal serotypes included in its formulation. However, one of them, the serotype 3 (ST3) is still being relatively commonly isolated from patients, suggesting an escape from vaccine-induced immunity.

Protection induced by Streptococcus pneumoniae extracellular vesicles against nasal colonization and invasive infection in mice and the role of PspA.

Diseases caused by Streptococcus pneumoniae (pneumococcus) produce a great impact on public health, killing about one million people annually despite available vaccines. Recent research has revealed that the pneumococcus produces extracellular vesicles (pEVs), which display selective cargo and hold potential for vaccine development. Here, we evaluated the immunogenicity and protective potential of pEVs derived from a non-encapsulated pneumococcal strain (R6) using murine models of pneumococcal colonization and invasive pneumonia.

Negligible role for pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC) in the nasopharyngeal colonization of mice with a serotype 6B pneumococcal strain.

Streptococcus pneumoniae colonizes the human nasopharynx asymptomatically, but it can also cause several diseases, including otitis media, pneumonia, bacteremia, and meningitis. The colonization of the nasopharynx by the bacteria is an essential step for the pneumococcus to invade other sites and cause diseases. Pneumococcal surface protein A (PspA) and Pneumococcal surface Protein C (PspC) are important virulence factors and have been described to play roles in adhesion and immune evasion.

Long non-coding RNAs are essential for Schistosoma mansoni pairing-dependent adult worm homeostasis and fertility.

The trematode parasite Schistosoma mansoni causes schistosomiasis, which affects over 200 million people worldwide. Schistosomes are dioecious, with egg laying depending on the females' obligatory pairing with males. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential that have been involved in other species with reproduction, stem cell maintenance, and drug resistance.

Pneumococcal Vaccines: Past Findings, Present Work, and Future Strategies.

The importance of has been well established. These bacteria can colonize infants and adults without symptoms, but in some cases can spread, invade other tissues and cause disease with high morbidity and mortality. The development of pneumococcal conjugate vaccines (PCV) caused an enormous impact in invasive pneumococcal disease and protected unvaccinated people by herd effect.

Serum levels of anti-PspA and anti-PspC IgG decrease with age and do not correlate with susceptibility to experimental human pneumococcal colonization.

Older adults are at increased risk of pneumococcal disease. This work aims to evaluate whether there is any decrease in serum IgG against variants of the antigens Pneumococcal surface protein A (PspA) and Pneumococcal surface protein C (PspC) in healthy adults with increasing age. Levels of IgG against PspA and PspC variants were determined by ELISA in serum samples comparing volunteers 18-30 years of age with volunteers who were 50-70+ before and after an experimental pneumococcal colonization challenge.

Efficacy of a Protein Vaccine and a Conjugate Vaccine Against Co-colonization with Vaccine-type and Non-vaccine Type Pneumococci in Mice.

Widespread use of pneumococcal conjugate vaccines (PCVs) has led to substitution of vaccine-type (VT) strains by non-vaccine type (NVT) strains in nasopharyngeal carriage. We compared the efficacy of PCV13 and a nasal protein formulation containing pneumococcal surface protein A (PspA) adjuvanted with the whole-cell pertussis vaccine (wP) in the protection against co-colonization challenge models in mice with VT and NVT strains expressing different PspAs. Immunized mice were challenged with two different mixtures: i.

Correction: Evaluation of inactivated Bordetella pertussis as a delivery system for the immunization of mice with Pneumococcal Surface Antigen A.

[This corrects the article DOI: 10.1371/journal.pone.

Evaluation of inactivated Bordetella pertussis as a delivery system for the immunization of mice with Pneumococcal Surface Antigen A.

Pneumococcal Surface Protein A (PspA) has been successfully tested as vaccine candidate against Streptococcus pneumoniae infections. Vaccines able to induce PspA-specific antibodies and Th1 cytokines usually provide protection in mice. We have shown that the whole cell pertussis vaccine (wP) or components from acellular pertussis vaccines, such as Pertussis Toxin or Filamentous Hemagglutinin (FHA), are good adjuvants to PspA, suggesting that combined pertussis-PspA vaccines would be interesting strategies against the two infections.

Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection.

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles-NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro).

Impaired expression of CXCL5 and matrix metalloproteinases in the lungs of mice with high susceptibility to Streptococcus pneumoniae infection.

Introduction: Streptococcus pneumoniae colonizes the nasopharynx of healthy individuals establishing a commensal relationship with the host. In some conditions, bacteria invade the lower respiratory tract and innate immune responses are crucial to avoid diseases such as pneumonia, sepsis, or meningitis.

Methods: Here, we compared the susceptibility to pneumococcal respiratory infection of two outbred mouse lines, AIRmin and AIRmax, selected for low or high acute inflammatory responses, respectively.

Protection Elicited by Nasal Immunization with Recombinant Pneumococcal Surface Protein A (rPspA) Adjuvanted with Whole-Cell Pertussis Vaccine (wP) against Co-Colonization of Mice with Streptococcus pneumoniae.

A promising alternative vaccine candidate to reduce the burden of pneumococcal diseases is the protein antigen PspA (Pneumococcal surface protein A). Since concomitant colonization with two or more pneumococcal strains is very common in children, we aimed to determine if immunization with PspA would be able to control co-colonization. We evaluated nasal immunization with recombinant PspA (rPspA) in a model of co-colonization with two strains expressing different PspAs.

Design, Immune Responses and Anti-Tumor Potential of an HPV16 E6E7 Multi-Epitope Vaccine.

Cervical cancer is a common type of cancer among women worldwide and infection with high-risk human papillomavirus (HPVs) types represents the major risk factor for the etiopathogenesis of the disease. HPV-16 is the most frequently identified HPV type in cervical lesions and expression of E6 and E7 oncoproteins is required for the uncontrolled cellular proliferation. In the present study we report the design and experimental testing of a recombinant multi-epitope protein containing immunogenic epitopes of HPV-16 E6 and E7.

Evaluation of a vaccine formulation against Streptococcus pneumoniae based on choline-binding proteins.

Streptococcus pneumoniae has proteins that are attached to its surface by binding to phosphorylcholine of teichoic and lipoteichoic acids. These proteins are known as choline-binding proteins (CBPs). CBPs are an interesting alternative for the development of a cost-effective vaccine, and PspA (pneumococcal surface protein A) is believed to be the most important protective component among the different CBPs.

Aerobic exercise attenuates pulmonary inflammation induced by Streptococcus pneumoniae.

Aerobic exercise has been recognized as a stimulator of the immune system, but its effect on bacterial infection has not been extensively evaluated. We studied whether moderate aerobic exercise training prior to Streptococcus pneumoniae infection influences pulmonary inflammatory responses. BALB/c mice were divided into four groups: Sedentary Untreated (sedentary without infection); Sedentary Infected (sedentary with infection); Trained Untreated (aerobic training without infection); and Trained Infected (aerobic training with infection).

Pertussis toxin improves immune responses to a combined pneumococcal antigen and leads to enhanced protection against Streptococcus pneumoniae.

Pneumococcal surface protein A (PspA) is a candidate antigen for the composition of protein-based vaccines against Streptococcus pneumoniae. While searching for efficient adjuvants for PspA-based vaccines, our group has described the potential of combining PspA with the whole-cell pertussis vaccine (wP). When given to mice through the nasal route, a formulation composed of PspA from clade 5 (PspA5) and wP (PspA5-wP) induced high levels of antibodies and protection against challenges with different pneumococcal strains.

Mapping of epitopes recognized by antibodies induced by immunization of mice with PspA and PspC.

Pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC) are important candidates for an alternative vaccine against pneumococcal infections. Since these antigens show variability, the use of variants that do not afford broad protection may lead to the selection of vaccine escape bacteria. Epitopes capable of inducing antibodies with broad cross-reactivities should thus be the preferred antigens.

Pneumococcal Surface Protein A does not affect the immune responses to a combined diphtheria tetanus and pertussis vaccine in mice.

The Pneumococcal Surface Protein A (PspA) is a promising candidate for the composition of a protein vaccine against Streptococcus pneumoniae. We have previously shown that the whole cell Bordetella pertussis vaccine (wP) is a good adjuvant to PspA, inducing protective responses against pneumococcal infection in mice. In Brazil, wP is administered to children, formulated with diphtheria and tetanus toxoids (DTPw) and aluminum hydroxide (alum) as adjuvant.

Characterization of the antibody response elicited by immunization with pneumococcal surface protein A (PspA) as recombinant protein or DNA vaccine and analysis of protection against an intranasal lethal challenge with Streptococcus pneumoniae.

Pneumococcal surface protein A (PspA) is an important candidate for a vaccine against pneumococcal infections. DNA vaccines expressing PspA were shown to protect mice against intraperitoneal and colonization challenge models in mice. We now show that a DNA vaccine expressing PspA from clade 4 (pSec-pspA4Pro) is also able to elicit protection against an intranasal lethal challenge model at levels similar to the recombinant protein PspA4Pro adjuvanted with alum.

Controlled inflammatory responses in the lungs are associated with protection elicited by a pneumococcal surface protein A-based vaccine against a lethal respiratory challenge with Streptococcus pneumoniae in mice.

Streptococcus pneumoniae is a pathogen of great importance worldwide. We have previously described the efficacy of a nasal vaccine composed of the pneumococcal surface protein A and the whole-cell pertussis vaccine as an adjuvant against a pneumococcal invasive challenge in mice. Spread of bacteria to the bloodstream was probably prevented by the high levels of systemic antibodies induced by the vaccine, but bacteria were only cleared from the lungs 3 weeks later, indicating that local immune responses may contribute to survival.

Cross-reactivity of antipneumococcal surface protein C (PspC) antibodies with different strains and evaluation of inhibition of human complement factor H and secretory IgA binding via PspC.

Pneumococcal surface protein C (PspC) is an important candidate for a cost-effective vaccine with broad coverage against pneumococcal diseases. Previous studies have shown that Streptococcus pneumoniae is able to bind to both human factor H (FH), an inhibitor of complement alternative pathway, and human secretory IgA (sIgA) via PspC. PspC was classified into 11 groups based on variations of the gene.

Lactic acid bacteria in the prevention of pneumococcal respiratory infection: future opportunities and challenges.

Lactic acid bacteria (LAB) are technologically and commercially important and have various beneficial effects on human health. Several studies have demonstrated that certain LAB strains can exert their beneficial effect on the host through their immunomudulatory activity. Although most research concerning LAB-mediated enhanced immune protection is focused on gastrointestinal tract pathogens, recent studies have centered on whether these immunobiotics might sufficiently stimulate the common mucosal immune system to provide protection to other mucosal sites as well.

Combination of pneumococcal surface protein A (PspA) with whole cell pertussis vaccine increases protection against pneumococcal challenge in mice.

Streptococcus pneumoniae is the leading cause of respiratory acute infections around the world. In Latin America, approximately 20,000 children under 5 years of age die of pneumococcal diseases annually. Pneumococcal surface protein A (PspA) is among the best-characterized pneumococcal antigens that confer protection in animal models of pneumococcal infections and, as such, is a good alternative for the currently available conjugated vaccines.

Protection against nasal colonization with Streptococcus pneumoniae by parenteral immunization with a DNA vaccine encoding PspA (Pneumococcal surface protein A).

Pneumococcal surface protein A (PspA) is an important candidate for a cost-effective vaccine with broad coverage against Streptococcus pneumoniae. We have previously shown that intramuscular immunization with PspA as a DNA vaccine induces an immune response characterized by the induction of a balanced IgG1/IgG2a antibody response in BALB/c mice, which was able to efficiently mediate complement deposition onto intact bacteria and to induce protection against an intraperitoneal challenge. We now confirm the results in C57BL/6 mice and further show that the response induced by the DNA vaccine expressing PspA is able to mediate protection against colonization of the nasopharyngeal mucosa even though immunization was given parenterally.

Immunization of mice with single PspA fragments induces antibodies capable of mediating complement deposition on different pneumococcal strains and cross-protection.

PspA is an important candidate for a vaccine with serotype-independent immunity against pneumococcal infections. Based on sequence relatedness, PspA has been classified into three families comprising six clades. We have previously addressed the cross-reactivity of antibodies against PspA fragments containing the N-terminal and proline-rich regions of PspA from clades 1 to 5 (PspA1, PspA2, PspA3, PspA4, and PspA5) by Western blot analysis and reported that anti-PspA4 and anti-PspA5 were able to recognize pneumococci expressing PspA proteins from all of the clades analyzed.