Characterization of Protective Mucosal and Systemic Immune Responses Elicited by Pneumococcal Surface Protein PspA and PspC Nasal Vaccines against a Respiratory Pneumococcal Challenge in Mice

Ferreira, Daniela M.; Darrieux, Michelle; Silva, D. A.; Leite, Luciana C. C.; Ferreira, Jorge M. C.; Ho, Paulo Lee; Miyaji, Eliane N.; Oliveira, Maria Leonor S.

doi:10.1128/cvi.00395-08

Cited by 105 publications

(118 citation statements)

References 50 publications

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“…In our results, mice from all groups responded quickly with TNF-␣ secretion in the respiratory mucosa, but strong control of this cytokine was observed only in protected mice. This is in agreement with previous results from our group that correlated increased protection against pneumococcal invasive challenge in mice with low levels of TNF-␣ secretion in the airways at 13 h after challenge (20). Secretion of IL-6, IFN-␥, and TNF-␣ in the respiratory mucosa was also followed for several days until complete pneumococcal clearance (21 days later), but the levels remained low in mice vaccinated with PspA5-wP at all time points tested (data not shown).…”

Section: Discussionsupporting

confidence: 83%

“…However, despite the presence of antibodies, complete clearance of bacteria from the lungs occurred only 3 weeks after the challenge, suggesting that immune responses in the respiratory mucosa may contribute to protection (43). The control of inflammatory responses in lungs seems to be an important feature for protection against pneumococcal respiratory invasive challenges in mice (20,21). Here we have evaluated the mucosal immune responses elicited in lungs of mice vaccinated with PspA5-wP.…”

mentioning

confidence: 99%

“…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). We have previously used the whole-cell pertussis vaccine (wP) as an adjuvant to a nasal vaccine formulated with an N-terminal fragment of PspA from clade 5 (PspA5-wP) (43).…”

mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 83%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…This key role for IL-17 against S. aureus skin infection has direct implications in future vaccine development, which may depend on the generation of IL-17-producing memory T cells at cutaneous sites. The critical role of vaccine-induced IL-17 at epithelial sites has been previously demonstrated against Helicobacter pylori gut infection and Mycobacterium tuberculosis, Streptococcus pneumonia, and Pseudomonas aeruginosa lung infections (58)(59)(60)(61). However, both IL-17-and IFN-γ-producing memory T cells may be required for vaccine protection against S. aureus at all sites of infection.…”

Section: Discussionmentioning

confidence: 99%

IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice

Cho¹,

Pietras²,

Garcia³

et al. 2010

J. Clin. Invest.

579

596

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Staphylococcus aureus is the most common cause of skin and soft tissue infections, and rapidly emerging antibiotic-resistant strains are creating a serious public health concern. If immune-based therapies are to be an alternative to antibiotics, greater understanding is needed of the protective immune response against S. aureus infection in the skin. Although neutrophil recruitment is required for immunity against S. aureus, a role for T cells has been suggested. Here, we used a mouse model of S. aureus cutaneous infection to investigate the contribution of T cells to host defense. We found that mice deficient in γδ but not αβ T cells had substantially larger skin lesions with higher bacterial counts and impaired neutrophil recruitment compared with WT mice. This neutrophil recruitment was dependent upon epidermal Vγ5 + γδ T cell production of IL-17, but not IL-21 and IL-22. Furthermore, IL-17 induction required IL-1, TLR2, and IL-23 and was critical for host defense, since IL-17R-deficient mice had a phenotype similar to that of γδ T cell-deficient mice. Importantly, γδ T cell-deficient mice inoculated with S. aureus and treated with a single dose of recombinant IL-17 had lesion sizes and bacterial counts resembling those of WT mice, demonstrating that IL-17 could restore the impaired immunity in these mice. Our study defines what we believe to be a novel role for IL-17-producing epidermal γδ T cells in innate immunity against S. aureus cutaneous infection.

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“…Indeed, it was reported that S. pneumoniae capsular polysaccharide-specific polymeric IgA Abs more efficiently initiated complement-mediated killing of the organism (37). Further, recent studies demonstrated that pIgR 2/2 mice that lack the ability to actively secrete polymeric IgA Abs onto mucosal surfaces failed to provide protection against nasal challenge with S. pneumoniae despite being given a mucosal vaccine that induced S-IgA Abs in normal mice (38)(39)(40). Although studies in pIgR 2/2 mice have suggested that S-IgA is the most important Ab isotype in mediating protection against pneumococcal infection, the work failed to provide direct evidence for a role for S. pneumoniae-specific IgA Ab responses, because pIgR 2/2 mice possessed detectable levels of IgA Abs in their mucosal secre- tions.…”

Section: Discussionmentioning

confidence: 99%

Secretory-IgA Antibodies Play an Important Role in the Immunity to Streptococcus pneumoniae

Fukuyama

King

Kataoka

et al. 2010

The Journal of Immunology

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This study was designed to investigate whether secretory-IgA (S-IgA) Abs induced by a pneumococcal surface protein A (PspA)-based nasal vaccine are necessary for prevention of streptococcal colonization. Mice nasally immunized with PspA plus a plasmid expressing Flt3 ligand (pFL) cDNA as a mucosal adjuvant showed significantly higher levels of PspA-specific S-IgA and IgG Ab responses in both plasma and nasal washes when compared with naive mice. Although IgA−/− mice given nasal PspA plus pFL had significantly high levels of PspA-specific IgG Abs, high numbers of CFUs were detected in nasal washes and nasal passages. In contrast, vaccinated wild-type mice showed essentially no bacteria in the nasal cavity. Further, a nasal vaccine consisting of PspA plus pFL effectively reduced pre-existing Streptococcus pneumoniae in the nasal cavity. These results show that PspA-based vaccine-induced specific S-IgA Abs play a necessary role in the regulation of S. pneumoniae colonization in the nasal cavity.

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Characterization of Protective Mucosal and Systemic Immune Responses Elicited by Pneumococcal Surface Protein PspA and PspC Nasal Vaccines against a Respiratory Pneumococcal Challenge in Mice

Cited by 105 publications

References 50 publications

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

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

IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice

Secretory-IgA Antibodies Play an Important Role in the Immunity to Streptococcus pneumoniae

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