Limited Efficacy of Antibacterial Vaccination Against Secondary Serotype 3 Pneumococcal Pneumonia Following Influenza Infection

Metzger, Dennis W.; Furuya, Yasubumi; Salmon, Sharon L.; Roberts, Sean; Sun, Keer

doi:10.1093/infdis/jiv066

Cited by 31 publications

(38 citation statements)

References 28 publications

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“…Although influenza virus and pneumococcus coinfection is responsible for higher mortality and morbidity, the current pneumococcal conjugate vaccine does not provide sufficient protection in the serial coinfection model (Metzger et al 2015). Therefore, the development of a new type of vaccine, which can protect against influenza virus and pneumococcus coinfection, is required.…”

Section: Factors Increasing Pneumonia Risk In Pneumococcal Infectionsmentioning

confidence: 99%

Pneumonia and Streptococcus pneumoniae vaccine

2017

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Pneumonia is an inflammatory disease of the lung, responsible for high morbidity and mortality worldwide. It is caused by bacteria, viruses, fungi, or other microorganisms. Streptococcus pneumoniae, a gram-positive bacterium with over 90 serotypes, is the most common causative agent. Moreover, comorbid factors including heart failure, renal disease, and pulmonary disease could increase the risk of pneumococcal pneumonia. Since the advent of the pneumococcal vaccine in the 1980s, the incidence of pneumonia has decreased significantly. However, current vaccines confer only limited protection against serotypes included in the vaccine. Thus, to overcome this limitation, new types of pneumococcal vaccines have been sought and under clinical trials. In this review, we discuss pneumonia and summarize the various types of pneumococcal vaccines in progress.

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Section: Factors Increasing Pneumonia Risk In Pneumococcal Infectionsmentioning

confidence: 99%

Pneumonia and Streptococcus pneumoniae vaccine

2017

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“…In contrast, following vaccination against IAV viral exposure may still impair host defenses sufficiently to promote bacterial superinfection, even in the absence of a clinically apparent viral infection. Interestingly, a recent report using a conjugate vaccine against S. pneumoniae showed that this vaccine did not result in 100% protection as obtained with the anti-M protein vaccine (Metzger et al, 2015 ). This indicates that there is still much to learn regarding the differences in the pathogenesis of IAV-bacterial superinfections and the contributions of vaccine-induced immunity in the context of polymicrobial infections.…”

Section: Mechanisms Of Iav-gas Superinfectionmentioning

confidence: 99%

The Association between Invasive Group A Streptococcal Diseases and Viral Respiratory Tract Infections

2016

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Viral infections of the upper respiratory tract are associated with a variety of invasive diseases caused by Streptococcus pyogenes, the group A streptococcus, including pneumonia, necrotizing fasciitis, toxic shock syndrome, and bacteremia. While these polymicrobial infections, or superinfections, are complex, progress has been made in understanding the molecular basis of disease. Areas of investigation have included the characterization of virus-induced changes in innate immunity, differences in bacterial adherence and internalization following viral infection, and the efficacy of vaccines in mitigating the morbidity and mortality of superinfections. Here, we briefly summarize viral-S. pyogenes superinfections with an emphasis on those affiliated with influenza viruses.

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“…SBIs, in particular, have accounted for 40–95 % of influenza-related mortality in past pandemics [4, 17, 29, 48]. Vaccines against bacterial pathogens can reduce the coinfection component [15, 25, 27], but their efficacy is limited to the vaccine strains and some bacterial vaccines have reduced effectiveness in influenza virus-infected hosts [25, 27]. Treatment with antimicrobial agents may also improve disease outcome and reduce SBI incidence [7, 8, 12, 13, 18, 21, 26], but many provide only partial protection, have time dependent efficacy, and/or cause adverse effects.…”

Section: Introductionmentioning

confidence: 99%

Quantifying the therapeutic requirements and potential for combination therapy to prevent bacterial coinfection during influenza

Smith

2016

J Pharmacokinet Pharmacodyn

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Secondary bacterial infections (SBIs) exacerbate influenza-associated disease and mortality. Antimicrobial agents can reduce the severity of SBIs, but many have limited efficacy or cause adverse effects. Thus, new treatment strategies are needed. Kinetic models describing the infection process can help determine optimal therapeutic targets, the time scale on which a drug will be most effective, and how infection dynamics will change under therapy. To understand how different therapies perturb the dynamics of influenza infection and bacterial coinfection and to quantify the benefit of increasing a drug’s efficacy or targeting a different infection process, I analyzed data from mice treated with an antiviral, an antibiotic, or an immune modulatory agent with kinetic models. The results suggest that antivirals targeting the viral life cycle are most efficacious in the first 2 days of infection, potentially because of an improved immune response, and that increasing the clearance of infected cells is important for treatment later in the infection. For a coinfection, immunotherapy could control low bacterial loads with as little as 20 % efficacy, but more effective drugs would be necessary for high bacterial loads. Antibiotics targeting bacterial replication and administered 10 h after infection would require 100 % efficacy, which could be reduced to 40 % with prophylaxis. Combining immunotherapy with antibiotics could substantially increase treatment success. Taken together, the results suggest when and why some therapies fail, determine the efficacy needed for successful treatment, identify potential immune effects, and show how the regulation of underlying mechanisms can be used to design new therapeutic strategies.Electronic supplementary materialThe online version of this article (doi:10.1007/s10928-016-9494-9) contains supplementary material, which is available to authorized users.

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Limited Efficacy of Antibacterial Vaccination Against Secondary Serotype 3 Pneumococcal Pneumonia Following Influenza Infection

Cited by 31 publications

References 28 publications

Pneumonia and Streptococcus pneumoniae vaccine

Pneumonia and Streptococcus pneumoniae vaccine

The Association between Invasive Group A Streptococcal Diseases and Viral Respiratory Tract Infections

Quantifying the therapeutic requirements and potential for combination therapy to prevent bacterial coinfection during influenza

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