Intranasal vaccination with pneumococcal surface protein A plus poly(I:C) protects against secondary pneumococcal pneumonia in mice

Ezoe, Hirokazu; Akeda, Yukihiro; Piao, Zhenyu; Aoshi, Taiki; Koyama, Shohei; Tanimoto, Tsuyoshi; Ishii, Ken J.; Oishi, Kazunori

doi:10.1016/j.vaccine.2010.12.117

Cited by 14 publications

(17 citation statements)

References 34 publications

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“…immunization with PspA administered in the presence of cholera toxin B subunit as an adjuvant or with polyinosinic-poly(C), a Toll-like receptor 3 agonist, reduced the bacterial load of pneumococci in the lungs of influenza A virus-infected mice. Yet neither strategy eradicated the pneumococci in the lungs (24,25). While these studies did not examine nasopharyngeal colonization, previous research suggested that mucosal immunization with PspA was protective against colonization of the nasopharynx (34,44).…”

Section: Discussionmentioning

confidence: 94%

“…PspA is an important virulence factor that is expressed by all clinical pneumococcal isolates and is essential for full virulence during local and invasive disease although its role during colonization is less clear (16)(17)(18)(19). Other studies have revealed that PspA, when employed as an immunogen in mouse models, protects against primary pneumococcal infection (20-23) and against pneumococcal challenge subsequent to a viral infection (24,25). The vast majority of these investigations, however, examined the protection offered by PspA immunization against invasive disease caused by challenge with planktonic, broth-grown pneumococci, which do not represent either the biofilm community of S. pneumoniae normally found residing in the nasopharynx prior to contact with IAV or the bacteria released from biofilms in response to virus infection (4).…”

mentioning

confidence: 99%

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Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

Greene

Marks

et al. 2016

Infect Immun

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dStreptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccinetype pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx.

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

Greene

Marks

et al. 2016

Infect Immun

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“…Indeed, poly (I:C) treatment in mice was associated with a rapid induction of inflammatory cytokines in the serum, including IL-6, IL-10, MCP-1, TNF-, IFN-, and IFN-, and selective increases in the numbers of NK (NK1.1(+)CD11b(+)) cells [382]. These effects make it an effective adjuvant for pneumococcal surface protein A vaccine against secondary pneumococcal pneumonia in mice [384].…”

Section: Rna-like Compoundsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…The cutoff value was determined by adding 3-fold standard deviations (SD) to the mean (i.e., mean ϩ 3 SD) of the OD values of samples from naive mice. PspA-specific antibody titers in nasal wash samples, BALF, and sera were determined by use of an ELISA as previously described (15). Microtiter plates were coated overnight at 4°C with 100 l of 1-g/ml PspA.…”

Section: Cellsmentioning

confidence: 99%

“…Moreover, anti-PspA antibodies have also been shown to prevent infection from strains with different serotypes (14). We previously reported that mice immunized with recombinant PspA protein in combination with polyinosinic-poly(C) [poly(I·C)], a Toll-like receptor (TLR) agonist, as an adjuvant were completely protected against secondary pneumococcal pneumonia after influenza virus infection (15). Moreover, in human trials, intramuscular immunization with the recombinant PspA protein induced cross-reactive antibodies to heterologous PspA (14).…”

mentioning

confidence: 99%

A Bivalent Vaccine Based on a Replication-Incompetent Influenza Virus Protects against Streptococcus pneumoniae and Influenza Virus Infection

Katsura

Piao

Iwatsuki‐Horimoto

et al. 2014

J Virol

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Streptococcus pneumoniae is a major causative pathogen in community-acquired pneumonia; together with influenza virus, it represents an important public health burden. Although vaccination is the most effective prophylaxis against these infectious agents, no single vaccine simultaneously provides protective immunity against both S. pneumoniae and influenza virus. Previously, we demonstrated that several replication-incompetent influenza viruses efficiently elicit IgG in serum and IgA in the upper and lower respiratory tracts. Here, we generated a replication-incompetent hemagglutinin knockout (HA-KO) influenza virus possessing the sequence for the antigenic region of pneumococcal surface protein A (PspA). Although this virus (HA-KO/ PspA virus) could replicate only in an HA-expressing cell line, it infected wild-type cells and expressed both viral proteins and PspA. PspA-and influenza virus-specific antibodies were detected in nasal wash and bronchoalveolar lavage fluids and in sera from mice intranasally inoculated with HA-KO/PspA virus, and mice inoculated with HA-KO/PspA virus were completely protected from lethal challenge with either S. pneumoniae or influenza virus. Further, bacterial colonization of the nasopharynx was prevented in mice immunized with HA-KO/PspA virus. These results indicate that HA-KO/PspA virus is a promising bivalent vaccine candidate that simultaneously confers protective immunity against both S. pneumoniae and influenza virus. We believe that this strategy offers a platform for the development of bivalent vaccines, based on replication-incompetent influenza virus, against pathogens that cause respiratory infectious diseases. IMPORTANCEStreptococcus pneumoniae and influenza viruses cause contagious diseases, but no single vaccine can simultaneously provide protective immunity against both pathogens. Here, we used reverse genetics to generate a replication-incompetent influenza virus carrying the sequence for the antigenic region of pneumococcal surface protein A and demonstrated that mice immunized with this virus were completely protected from lethal doses of infection with either influenza virus or Streptococcus pneumoniae. We believe that this strategy, which is based on a replication-incompetent influenza virus possessing the antigenic region of other respiratory pathogens, offers a platform for the development of bivalent vaccines.

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Intranasal vaccination with pneumococcal surface protein A plus poly(I:C) protects against secondary pneumococcal pneumonia in mice

Cited by 14 publications

References 34 publications

Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

Selection of Adjuvants for Enhanced Vaccine Potency

A Bivalent Vaccine Based on a Replication-Incompetent Influenza Virus Protects against Streptococcus pneumoniae and Influenza Virus Infection

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