Epidemiological Evidence for Serotype‐Independent Acquired Immunity to Pneumococcal Carriage

Granat, Simo; Ollgren, Jukka; Herva, Elja; Mia, Zakaria; Auranen, Kari; Mäkelä, P. Helena

doi:10.1086/599364

Cited by 45 publications

(48 citation statements)

References 42 publications

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“…Mice immunized with WT-BCG or rBCG Mix with or without a booster dose of rMix, rBCG 0148/rSP 0148, or rBCG 2108/rSP 2108 were challenged by intranasal inoculation with the virulent serotype 3 pneumococcal strain WU2 (32) while the mice were under anesthesia. Mice that received saline and Al(OH) 3 were used as a control. In this model, mice aspirate the inoculum into the lungs and develop illness by the third day after infection.…”

Section: Resultsmentioning

confidence: 99%

A Combination of Recombinant Mycobacterium bovis BCG Strains Expressing Pneumococcal Proteins Induces Cellular and Humoral Immune Responses and Protects against Pneumococcal Colonization and Sepsis

Goulart

Rodríguez

Kanno

et al. 2017

Clin Vaccine Immunol

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Pneumococcal diseases remain a substantial cause of mortality in young children in developing countries. The development of potentially serotypetranscending vaccines has been extensively studied; ideally, such a vaccine should include antigens that are able to induce protection against colonization (likely mediated by interleukin-17A [IL-17A]) and invasive disease (likely mediated by antibody). The use of strong adjuvants or alternative delivery systems that are able to improve the immunological response of recombinant proteins has been proposed but poses potential safety and practical concerns in children. We have previously constructed a recombinant Mycobacterium bovis BCG strain expressing a pneumococcal surface protein A (PspA)-PdT fusion protein (rBCG PspA-PdT) that was able to induce an effective immune response and protection against sepsis in a prime-boost strategy. Here, we constructed two new rBCG strains expressing the pneumococcal proteins SP 0148 and SP 2108, which confer IL-17A-dependent protection against pneumococcal colonization in mouse models. Immunization of mice with rBCG 0148 or rBCG 2108 in a prime-boost strategy induced IL-17A and gamma interferon (IFN-␥) production. The combination of these rBCG strains with rBCG PspA-PdT (rBCG Mix), followed by a booster dose of the combined recombinant proteins (rMix) induced an IL-17A response against SP 0148 and SP 2108 and a humoral response characterized by increased levels of IgG2c against PspA and functional antibodies against pneumolysin. Furthermore, immunization with the rBCG Mix prime/rMix booster (rBCG Mix/ rMix) provides protection against pneumococcal colonization and sepsis. These results suggest the use of combined rBCG strains as a potentially serotype-transcending pneumococcal vaccine in a prime-boost strategy, which could provide protection against pneumococcal colonization and sepsis.KEYWORDS protection, Streptococcus pneumoniae, cytokines, recombinant BCG N asopharynx colonization is the first step in the establishment of pneumococcal disease. This colonization process, which affects virtually 100% of young children, can either remain asymptomatic or lead to pathogenic conditions, such as otitis, sinusitis, pneumonia, meningitis, or sepsis (1). Indeed, epidemiologic evidence suggests that in response to pneumococcal carriage, both serotype-specific and -independent immunity to subsequent carriage develop (2, 3).Pneumococcal vaccines available are based on pure polysaccharides or polysaccha-

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Section: Resultsmentioning

confidence: 99%

A Combination of Recombinant Mycobacterium bovis BCG Strains Expressing Pneumococcal Proteins Induces Cellular and Humoral Immune Responses and Protects against Pneumococcal Colonization and Sepsis

Goulart

Rodríguez

Kanno

et al. 2017

Clin Vaccine Immunol

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“…Epidemiological studies have suggested that immunity to pneumococcal colonization and disease develops in a manner that is not specific for the pneumococcal capsular serotype (7,14). To assess whether different pneumococcal serotypes induce distinct T helper cytokine profiles in the same donor, we infected cocultures with strains belonging to four different pneumococcal serotypes (2, 4, 9V, and 14) and measured IFN-␥ and IL-17 levels in the supernatants.…”

Section: Resultsmentioning

confidence: 99%

Human Monocytes Promote Th1 and Th17 Responses to Streptococcus pneumoniae

et al. 2011

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Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children. Human immunity to pneumococcal infections has been assumed to depend on anticapsular antibodies. However, recent findings from murine models suggest that alternative mechanisms, dependent on T helper cells, are also involved. Although the immunological events in which T helper cells contribute to acquired immunity have been studied in mice, little is known about how these responses are generated in humans. Therefore, we examined bacterial and host factors involved in the induction of Th1 and Th17 responses, using a coculture model of human monocytes and CD4 ؉ T cells. We show that monocytes promote effector cytokine production by memory T helper cells, leading to a mixed Th1/Th17 (gamma interferon [IFN-␥]/interleukin-17 [IL-17])profile. Both T helper cytokines were triggered by purified pneumococcal peptidoglycan; however, the balance between the two immune effector arms depended on bacterial viability. Accordingly, live pneumococci triggered a Th1-biased response via monocyte production of IL-12p40, whereas heat-killed pneumococci triggered a Th17 response through TLR2 signaling. An increased understanding of human T helper responses is essential for the development of novel pneumococcal vaccines designed to elicit cell-mediated immunity.

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“…Naturally acquired immunity is multifactorial; nonspecific antipneumococcal immunity develops alongside serotype-specific immunity in children through mechanisms that have not been entirely elucidated (34). In young infants with immature anti-CPS responses, epidemiological studies have suggested that nonspecific immunity predominates (35), while serotype-specific immunity comes to the fore in older children (32). In adulthood, both epidemiologic and controlled human infection studies have suggested that serotype-specific immunity plays a major role (33,36).…”

Section: Pneumococcal Colonization and Naturally Acquired Antipneumocmentioning

confidence: 99%

Pneumococcal Capsular Polysaccharide Immunity in the Elderly

Adler

Ferreira

Gordon

et al. 2017

Clin Vaccine Immunol

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Immunity to pneumococcal infections is impaired in older people, and current vaccines are poorly protective against pneumococcal disease in this population. Naturally acquired immunity to pneumococcal capsular polysaccharides develops during childhood and is robust in young adults but deteriorates with advanced age. In particular, antibody levels and function are reduced in older people. Pneumococcal vaccines are recommended for people Ͼ65 years old. However, the benefits of polysaccharide and protein-conjugated vaccines in this population are small, because of both serotype replacement and incomplete protection against vaccine serotype pneumococcal disease. In this review, we overview the immune mechanisms by which naturally acquired and vaccine-induced pneumococcal capsular polysaccharide immunity declines with age, including altered colonization dynamics, reduced opsonic activity of antibodies (particularly IgM), and impaired mucosal immunity.

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Epidemiological Evidence for Serotype‐Independent Acquired Immunity to Pneumococcal Carriage

Cited by 45 publications

References 42 publications

A Combination of Recombinant Mycobacterium bovis BCG Strains Expressing Pneumococcal Proteins Induces Cellular and Humoral Immune Responses and Protects against Pneumococcal Colonization and Sepsis

A Combination of Recombinant Mycobacterium bovis BCG Strains Expressing Pneumococcal Proteins Induces Cellular and Humoral Immune Responses and Protects against Pneumococcal Colonization and Sepsis

Human Monocytes Promote Th1 and Th17 Responses to Streptococcus pneumoniae

Pneumococcal Capsular Polysaccharide Immunity in the Elderly

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