Nasal immunization of mice with Lactobacillus casei expressing the Pneumococcal Surface Protein A: induction of antibodies, complement deposition and partial protection against Streptococcus pneumoniae challenge

Campos, Ivana Barros de; Darrieux, Michelle; Ferreira, Daniela M.; Miyaji, Eliane N.; Silva, Débora A.; Arêas, Ana Paula Mattos; Aires, Karina Araújo; Leite, Luciana C. C.; Ho, Paulo Lee; Oliveira, Maria Leonor S.

doi:10.1016/j.micinf.2008.01.007

Cited by 59 publications

(57 citation statements)

References 30 publications

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“…Gram-positive pathogenic bacteria express specific surface proteins that can interact with the components of the host extracellular matrix (6,23,31), adhere to host cells (35,47), invade, and evade host defenses (9,16,18,41). Cell wall-anchored surface proteins in streptococci usually contain a characteristic carboxyterminal sorting signal made of a conserved LPXTG motif.…”

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confidence: 99%

Fhb, a Novel Factor H-Binding Surface Protein, Contributes to the Antiphagocytic Ability and Virulence of Streptococcus suis

et al. 2012

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ABSTRACTStreptococcus suisserotype 2 is a Gram-positive bacterium that causes sepsis and meningitis in piglets and humans. The mechanisms ofS. suisserotype 2 invasive disease are not well understood. The surface proteins of pathogens usually play important roles in infection and bacterium-host interactions. Here, we identified a novel surface protein that contributed significantly to the virulence ofS. suisserotype 2 in a piglet infection model. This protein showed little similarity to other reported proteins and exhibited strong binding activity to human factor H (hFH). It was designated Fhb (factor H-binding protein). Thefhbgenes found inS. suisserotypes 1, 2, 4, 7, and 9 exhibited molecular polymorphism. Fhb possessed two proline-rich repeat sequences and XPZ domains, and one repeat sequence exhibited a high homology to Bac, an IgA-binding protein ofStreptococcus agalactiae. Evidence strongly indicated thatfhb-deficient mutants had diminished phagocytosis resistance in bactericidal assays. In addition, Fhb plays important roles in complement-mediated immunity by interacting with hFH. These findings indicated that Fhb is a crucial surface protein contributing to the virulence ofS. suis, with important functions in evading innate immune defenses by interaction with host complement regulatory factor hFH.

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confidence: 99%

Fhb, a Novel Factor H-Binding Surface Protein, Contributes to the Antiphagocytic Ability and Virulence of Streptococcus suis

et al. 2012

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“…Different immunization strategies and animal models were used to confirm PspA as a good vaccine candidate (4,12,36,57). This antigen has already undergone a phase I clinical trial and was shown to be immunogenic in humans (38).…”

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confidence: 99%

“…Broad-coverage vaccines based on PspA would thus depend on the use of more than one molecule or on the choice of specific PspA molecules (37). In animal models, protection elicited by vaccines composed of PspA is often accompanied by the induction of high levels of specific antibodies (10,22,24,44) which, upon binding to pneumococcal surface, promote the deposition of complement (9,12,47,57) and enhance killing by lactoferrin (9,48). In addition, the use of adjuvants that elicit Th1 immune responses against PspA seems to optimize protection (4,19,20).…”

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confidence: 99%

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

Lima

Ferreira

Moreno

et al. 2012

Clin Vaccine Immunol

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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. Here we show that a strict control of inflammatory responses in lungs of vaccinated mice occurs even in the presence of high numbers of pneumococci. This response was characterized by a sharp peak of neutrophils and lymphocytes with a simultaneous decrease in macrophages in the respiratory mucosa at 12 h postchallenge. Secretion of interleukin-6 (IL-6) and gamma interferon (IFN-␥) was reduced at 24 h postchallenge, and the induction of tumor necrosis factor alpha (TNF-␣) secretion, observed in the first hours postchallenge, was completely abolished at 24 h. Before challenge and at 12 h postchallenge, vaccinated mice displayed higher numbers of CD4 ؉ T, CD8 ؉ T, and B lymphocytes in the lungs. However, protection still occurs in the absence of each of these cells during the challenge, indicating that other effectors may be related to the prevention of lung injuries in this model. High levels of mucosal anti-PspA antibodies were maintained in vaccinated mice during the challenge, suggesting an important role in protection.

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“…117 The LAB, Lactobacillus casei, has been developed as an intranasal vaccine which expresses the S. pneumoniae protein antigen PspA and induces antibodies that protect mice from a systemic challenge. 118 Another LAB, Lactococcus lactis, has also been used to express S. pneumoniae protein antigens including PspA, PpmA, PsaA, PppA, and SlrA 119 or serotype 3 120 and serotype 14 121 capsular polysaccharides. Colonization with the L. lactis strains expressing S. pneumoniae capsules led to the induction of specific IgG and IgM antibodies.…”

Section: Heterologous Expression Of Protective Antigensmentioning

confidence: 99%

The new first-line defense: the potential of nasopharyngeal colonization in vaccine strategies

Chan¹,

Cohen²,

Brown³

2016

VDT

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Abstract:Pathogens that can colonize the upper respiratory tract include Streptococcus pneumoniae, Hemophilus influenzae, Neisseria meningitidis, Moraxella catarrhalis, and Staphylococcus aureus. While these pathogens commonly asymptomatically colonize the nasopharynx of healthy adults, disease progression may occur in some individuals. In addition to these respiratory pathogens, there are a large number of commensal species also found in the upper respiratory tract which only very rarely cause disease, creating a complex community of bacterial species in the nasopharynx. This review addresses the novel, potential strategies that utilize the interactions between both homologous and heterologous species in the nasopharynx to vaccinate individuals against pathogenic bacteria. These strategies include the mechanisms employed by colonizing bacteria to regulate the presence of other species in the nasopharynx and the effect that colonization of the nasopharynx has on the host immune response. Interventional strategies investigated so far include the introduction of nonpathogenic bacteria to the nasopharynx to immunize against a closely related species, controlled colonization using both wild-type and attenuated species, and the use of other nonpathogenic colonizers to express antigens from potential pathogens. All these approaches harness the ability of the colonization to induce a mucosal immune response that can protect against future infection. In this review, S. pneumoniae and N. meningitidis colonization are used as case studies for this approach as the immunological effects of colonization have been widely studied in animal and human models. Colonization-based strategies have great potential, and, in particular, the attenuated strain approach has produced some encouraging data in animal models. However, the strategy for attenuating virulence must be stringent and caused by highly stable mutations that are unlikely to revert. In addition, the consequences of artificial administration of genetically modified bacteria to the nasopharynx on the usual host microbiome are unknown and would need to be monitored carefully.

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Nasal immunization of mice with Lactobacillus casei expressing the Pneumococcal Surface Protein A: induction of antibodies, complement deposition and partial protection against Streptococcus pneumoniae challenge

Cited by 59 publications

References 30 publications

Fhb, a Novel Factor H-Binding Surface Protein, Contributes to the Antiphagocytic Ability and Virulence of Streptococcus suis

Fhb, a Novel Factor H-Binding Surface Protein, Contributes to the Antiphagocytic Ability and Virulence of Streptococcus suis

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

The new first-line defense: the potential of nasopharyngeal colonization in vaccine strategies

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