Interaction between the nasal microbiota and S. pneumoniae in the context of live-attenuated influenza vaccine

Piters, Wouter A A de Steenhuijsen; Jochems, Simon P.; Mitsi, Elena; Rylance, Jamie; Pojar, Sherin; Nikolaou, Elissavet; German, Esther L.; Holloway, M. Katharine; Carniel, Beatriz F.; Chu, Mei Ling J N; Arp, Kayleigh; Sanders, Elisabeth A. M.; Ferreira, Daniela M.; Bogaert, Debby

doi:10.1038/s41467-019-10814-9

Cited by 64 publications

(58 citation statements)

References 45 publications

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“…If the process of healthy and timely colonization is disrupted, early-life dysbiosis of the gut and lung microbiota becomes an important risk factor for the development of many respiratory diseases (Biesbroek et al, 2014;Teo et al, 2015). The mechanisms involved likely operate at different modes e.g., via inadequate training of host immunity , inefficient colonization resistance (de Steenhuijsen Piters et al, 2019), and/or improper lung morphogenesis (Yun et al, 2014). During in utero development and later in life, there are several direct and indirect factors that affect healthy microbiota colonization and subsequent host-microbiota interactions.…”

Section: Asthma Is Not a Single Diseasementioning

confidence: 99%

The Role of Lung and Gut Microbiota in the Pathology of Asthma

et al. 2020

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Section: Asthma Is Not a Single Diseasementioning

confidence: 99%

The Role of Lung and Gut Microbiota in the Pathology of Asthma

et al. 2020

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“…Albeit, there have been conflicting results regarding the impact of influenza infection on the respiratory tract microbiome (67,68). Yet, both murine and recent human studies agree that an initial influenza (or live-attenuated vaccine) exposure increases susceptibility to secondary (or colonizing) S. pneumoniae (69,70).…”

Section: Viral-bacterial Co-infection In the Lungmentioning

confidence: 99%

Inflammation as a Modulator of Host Susceptibility to Pulmonary Influenza, Pneumococcal, and Co-Infections

Aguilera

Lenz

2020

Front. Immunol.

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Bacterial and viral pathogens are predominant causes of pulmonary infections and complications. Morbidity and mortality from these infections is increased in populations that include the elderly, infants, and individuals with genetic disorders such as Down syndrome. Immune senescence, concurrent infections, and other immune alterations occur in these susceptible populations, but the underlying mechanisms that dictate increased susceptibility to lung infections are not fully defined. Here, we review unique features of the lung as a mucosal epithelial tissue and aspects of inflammatory and immune responses in model pulmonary infections and co-infections by influenza virus and Streptococcus pneumoniae. In these models, lung inflammatory responses are a double-edged sword: recruitment of immune effectors is essential to eliminate bacteria and virus-infected cells, but inflammatory cytokines drive changes in the lung conducive to increased pathogen replication. Excessive accumulation of inflammatory cells also hinders lung function, possibly causing death of the host. Some animal studies have found that targeting host modulators of lung inflammatory responses has therapeutic or prophylactic effects in these infection and co-infection models. However, conflicting results from other studies suggest microbiota, sequence of colonization, or other unappreciated aspects of lung biology also play important roles in the outcome of infections. Regardless, a predisposition to excessive or aberrant inflammatory responses occurs in susceptible human populations. Hence, in appropriate contexts, modulation of inflammatory responses may prove effective for reducing the frequency or severity of pulmonary infections. However, there remain limitations in our understanding of how this might best be achieved-particularly in diverse human populations.

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“…• Cytokine profiles -measurement of cytokines will be done on nasosorption and serum samples using multiplex bead array as previously reported 18 . This will enable us to identify potential soluble marker correlates of protection against pneumococcal colonisation.…”

Section: Immunological Assaysmentioning

confidence: 99%

A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi – A feasibility study

et al. 2020

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Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement and demonstrate reduced effectiveness against mucosal colonisation. As asymptomatic colonisation of the human nasopharynx is a prerequisite for pneumococcal disease, this is proposed as a marker for novel vaccine efficacy. Our team established a safe and reproducible pneumococcal controlled human infection model at Liverpool School of Tropical Medicine (LSTM). This has been used to test vaccine induced protection against nasopharyngeal carriage for ten years in over 1000 participants. We will transfer established standardised operating procedures from LSTM to Malawi and test in up to 36 healthy participants. Primary endpoint: detection of the inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: confirmation of robust clinical and laboratory methods for sample capture and processing. Tertiary endpoints: participant acceptability of study and methods. We will test three doses of pneumococcal inoculation (20,000, 80,000 and 160,000 colony forming units [CFUs] per naris) using a parsimonious study design intended to reduce unnecessary exposure to participants. We hypothesise that 80,000 CFUs will induce nasal colonisation in approximately half of participants per established LSTM practice. The aims of the feasibility study are: 1) Establish Streptococcus pneumoniae experimental human pneumococcal carriage in Malawi; 2) Confirm optimal nasopharyngeal pneumococcal challenge dose; 3) Confirm safety and measure potential symptoms; 4) Confirm sampling protocols and laboratory assays; 5) Assess feasibility and acceptability of consent and study procedures. Confirmation of pneumococcal controlled human infection model feasibility in Malawi will enable us to target pneumococcal vaccine candidates for an at-risk population who stand the most to gain from new and improved vaccine strategies.

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Interaction between the nasal microbiota and S. pneumoniae in the context of live-attenuated influenza vaccine

Cited by 64 publications

References 45 publications

The Role of Lung and Gut Microbiota in the Pathology of Asthma

The Role of Lung and Gut Microbiota in the Pathology of Asthma

Inflammation as a Modulator of Host Susceptibility to Pulmonary Influenza, Pneumococcal, and Co-Infections

A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi – A feasibility study

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