Pneumococcal colonization impairs nasal and lung mucosal immune responses to Live Attenuated Influenza Vaccination in adults

Bf, Carniel; Marcon, Fernando; Rylance, Jamie; Zaidi, Seher; Reiné, Jesús; Negera, Edessa; Nikolaou, Elissavet; Pojar, Sherin; Solórzano, Carla; Collins, Andrea; Connor,; Bogaert, Debby; Gordon, Stephen B.; Nakaya, Helder I.; Ferreira, DM; Jochems, Simon P.; Mitsi, Elena

doi:10.1101/2020.02.24.20025098

Cited by 6 publications

(8 citation statements)

References 65 publications

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“…In contrast, if vaccinees carry pneumococci at the time of vaccination, the protection conferred by live attenuated viral vaccines may be reduced. Interestingly, a recent human challenge study found that the immune response to live attenuated influenza vaccine was impaired in adults colonized with pneumococci ( 80 ), with some evidence for reduced viral loads (as inferred from qPCR threshold cycle [ C T ] values) in colonized individuals.…”

Section: Discussionmentioning

confidence: 99%

Synergism and Antagonism of Bacterial-Viral Coinfection in the Upper Respiratory Tract

Manna

McAuley

Jacobson

et al. 2022

mSphere

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Section: Discussionmentioning

confidence: 99%

Synergism and Antagonism of Bacterial-Viral Coinfection in the Upper Respiratory Tract

Manna

McAuley

Jacobson

et al. 2022

mSphere

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“…S3 A and B). During experimental human pneumococcal colonization studies in healthy adults, carriage was associated with increased IFNA and IFNB gene expression in the respiratory epithelium ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Type I Interferon Signaling Is a Common Factor Driving Streptococcus pneumoniae and Influenza A Virus Shedding and Transmission

Zangari

Ortigoza

Lokken-Toyli

et al. 2021

mBio

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The dynamics underlying respiratory contagion (the transmission of infectious agents from the airways) are poorly understood. We investigated host factors involved in the transmission of the leading respiratory pathogen Streptococcus pneumoniae. Using an infant mouse model, we examined whether S. pneumoniae triggers inflammatory pathways shared by influenza A virus (IAV) to promote nasal secretions and shedding from the upper respiratory tract to facilitate transit to new hosts. Here, we show that amplification of the type I interferon (IFN-I) response is a critical host factor in this process, as shedding and transmission by both IAV and S. pneumoniae were decreased in pups lacking the common IFN-I receptor (Ifnar1−/− mice). Additionally, providing exogenous recombinant IFN-I to S. pneumoniae-infected pups was sufficient to increase bacterial shedding. The expression of IFN-stimulated genes (ISGs) was upregulated in S. pneumoniae-infected wild-type (WT) but not Ifnar1−/− mice, including genes involved in mucin type O-glycan biosynthesis; this correlated with an increase in secretions in S. pneumoniae- and IAV-infected WT compared to Ifnar1−/− pups. S. pneumoniae stimulation of ISGs was largely dependent on its pore-forming toxin, pneumolysin, and coinfection with IAV and S. pneumoniae resulted in synergistic increases in ISG expression. We conclude that the induction of IFN-I signaling appears to be a common factor driving viral and bacterial respiratory contagion. IMPORTANCE Respiratory tract infections are a leading cause of childhood mortality and, globally, Streptococcus pneumoniae is the leading cause of mortality due to pneumonia. Transmission of S. pneumoniae primarily occurs through direct contact with respiratory secretions, although the host and bacterial factors underlying transmission are poorly understood. We examined transmission dynamics of S. pneumoniae in an infant mouse model and here show that S. pneumoniae colonization of the upper respiratory tract stimulates host inflammatory pathways commonly associated with viral infections. Amplification of this response was shown to be a critical host factor driving shedding and transmission of both S. pneumoniae and influenza A virus, with infection stimulating expression of a wide variety of genes, including those involved in the biosynthesis of mucin, a major component of respiratory secretions. Our findings suggest a mechanism facilitating S. pneumoniae contagion that is shared by viral infection.

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“…Individuals shedding respiratory viruses-including influenza virus, respiratory syncytial virus (RSV), adenoviruses, endemic human coronaviruses (HCoVs), and human rhinoviruses [5][6][7][8][9][10][11]-have higherdensity pneumococcal carriage than individuals without respiratory virus infection. Additionally, pneumococcal carriers have diminished mucosal antibody responses to influenza virus challenge [12], and higher likelihood of both acquiring respiratory viruses and thereafter experiencing acute respiratory symptoms [13]. Whereas these interactions have been shown to promote transmission of both pneumococci and viruses [14,15], clinical implications including impacts on viral disease pathogenesis remain less clearly understood [16].…”

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confidence: 99%

Prevention of Coronavirus Disease 2019 Among Older Adults Receiving Pneumococcal Conjugate Vaccine Suggests Interactions Between Streptococcus pneumoniae and Severe Acute Respiratory Syndrome Coronavirus 2 in the Respiratory Tract

Lewnard

Bruxvoort

Fischer

et al. 2021

The Journal of Infectious Diseases

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Introduction While secondary pneumococcal pneumonia occurs less commonly after COVID-19 than after other viral infections, it remains unclear whether other interactions occur between SARS-CoV-2 and Streptococcus pneumoniae. Methods We probed potential interactions between these pathogens among adults aged ≥65y by measuring associations of COVID-19 outcomes with pneumococcal vaccination (13-valent conjugate and 23-valent polysaccharide; PCV13, PPSV23). We estimated adjusted hazard ratios (aHRs) using Cox proportional hazards models with doubly-robust inverse-propensity weighting. We assessed effect modification by antibiotic exposure to further test the biologic plausibility of a causal role for pneumococci. Results Among 531,033 adults, there were 3,677 COVID-19 diagnoses, leading to 1,075 hospitalizations and 334 fatalities, between 1 March-22 July, 2020. Estimated aHRs for COVID-19 diagnosis, hospitalization, and mortality associated with prior PCV13 receipt were 0.65 (95% confidence interval: 0.59-0.72), 0.68 (0.57-0.83), and 0.68 (0.49-0.95), respectively. Prior PPSV23 receipt was not associated with protection against the three outcomes. COVID-19 diagnosis was not associated with prior PCV13 within 90 days following antibiotic receipt, whereas aHR estimates were 0.65 (0.50-0.84) and 0.62 (0.56-0.70) during risk periods 91-365d and >365d following antibiotic receipt, respectively. Discussion Reduced risk of COVID-19 among PCV13 recipients, transiently attenuated by antibiotic exposure, suggests pneumococci may interact with SARS-CoV-2.

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Pneumococcal colonization impairs nasal and lung mucosal immune responses to Live Attenuated Influenza Vaccination in adults

Cited by 6 publications

References 65 publications

Synergism and Antagonism of Bacterial-Viral Coinfection in the Upper Respiratory Tract

Synergism and Antagonism of Bacterial-Viral Coinfection in the Upper Respiratory Tract

Type I Interferon Signaling Is a Common Factor Driving Streptococcus pneumoniae and Influenza A Virus Shedding and Transmission

Prevention of Coronavirus Disease 2019 Among Older Adults Receiving Pneumococcal Conjugate Vaccine Suggests Interactions Between Streptococcus pneumoniae and Severe Acute Respiratory Syndrome Coronavirus 2 in the Respiratory Tract

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