Pneumococcal Capsular Polysaccharide Immunity in the Elderly

Adler, Hugh; Ferreira, Daniela M.; Gordon, Stephen B.; Rylance, Jamie

doi:10.1128/cvi.00004-17

Cited by 35 publications

(36 citation statements)

References 114 publications

(128 reference statements)

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“…This is surprising given that the nasopharynx, a non-sterile environment extensively colonized by a diverse bacterial flora, is the first location encountered by IAV. Since Spn carriage is highest in children (36, 37), Spn colonization often precedes IAV infection in childhood (38, 39). Given that infant mice support efficient Spn colonization in the URT (25, 40), we investigated the impact of Spn colonization on IAV transmission.…”

Section: Resultsmentioning

confidence: 99%

An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae

Ortigoza

Blaser

Zafar

et al. 2018

Preprint

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1 9 2 0 2 1 2 2 Word count: Abstract (368), Text (4692) 2 3 2 ABSTRACT 2 4 2 5The pandemic potential of influenza A viruses (IAV) depends on the infectivity of 2 6 the host, transmissibility of the virus, and susceptibility of the recipient. While virus traits 2 7 supporting IAV transmission have been studied in detail using ferret and guinea pig 2 8 models, there is limited understanding of host traits determining transmissibility and 2 9 susceptibility because current animal models of transmission are not sufficiently 3 0 tractable. Although mice remain the primary model to study IAV immunity and 3 1 pathogenesis, the efficiency of IAV transmission in adult mice has been inconsistent. 2Here we describe an infant mouse model which support efficient transmission of IAV. 3We demonstrate that transmission in this model requires young age, close contact, 3 4 shedding of virus particles from the upper respiratory tract (URT) of infected pups, the 3 5 use of a transmissible virus strain, and a susceptible recipient. We characterize 3 6shedding as a marker of infectiousness that predicts the efficiency of transmission 3 7 among different influenza virus strains. We also demonstrate that transmissibility and 3 8 susceptibility to IAV can be inhibited by humoral immunity via maternal-infant transfer of 3 9 IAV-specific immunoglobulins, and modifications to the URT milieu, via sialidase activity 4 0 of colonizing Streptococcus pneumoniae (Spn). Due to its simplicity and efficiency, this 4 1 model can be used to dissect the host's contribution to IAV transmission and explore 4 2 new methods to limit contagion.4 3 3 IMPORTANCE 4 4 4 5This study provides insight into the role of the virus strain, age, immunity, and 4 6 URT flora on IAV shedding and transmission efficiency. Using the infant mouse model, 4 7 we found that: (a) differences in viral shedding of various IAV strains is dependent on 4 8 specific hemagglutinin (HA) and/or neuraminidase (NA) proteins; (b) host age plays a 4 9 key role in the efficiency of IAV transmission; (c) levels of IAV-specific immunoglobulins 5 0 are necessary to limit infectiousness, transmission, and susceptibility to IAV; and (d) 5 1 expression of sialidases by colonizing Spn antagonize transmission by limiting the 5 2 acquisition of IAV in recipient hosts. Our findings highlight the need for strategies that 5 3 limit IAV shedding, and the importance of understanding the function of the URT 5 4 bacterial composition in IAV transmission. This work reinforces the significance of a 5 5tractable animal model to study both viral and host traits affecting IAV contagion, and its 5 6 potential for optimizing vaccines and therapeutics that target disease spread. 5 7 5 8 5 9

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Section: Resultsmentioning

confidence: 99%

An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae

Ortigoza

Blaser

Zafar

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…20%). Study results vary greatly, due to differences in detection methods and sampling sites (118). In the nasopharynx S. pneumoniae interferes with host responses, such as the complement system, the recruitment of neutrophils and the protective mucus layer and competes/interacts with the local microbiome (119).…”

Section: Streptococcus Pneumoniae: Targeting Different Serotypes Of Amentioning

confidence: 99%

“…This is probably due to a lack of IgM antibodies with opsonizing function as IgM-producing memory B cells decline with age (127). Naturally acquired humoral immune responses also decline with age, particularly when measured by OPA (118). In some cases, cross-reactivity of antibodies with other serotypes can be seen in ELISA-assays (e.g., anti-19F antibodies elicited by PCV-7 binding serotype 19A polysaccharides), but not in OPA.…”

Section: Streptococcus Pneumoniae: Targeting Different Serotypes Of Amentioning

confidence: 99%

Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives

Wagner

Weinberger

2020

Front. Immunol.

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Infectious diseases are a major cause for morbidity and mortality in the older population. Demographic changes will lead to increasing numbers of older persons over the next decades. Prevention of infections becomes increasingly important to ensure healthy aging for the individual, and to alleviate the socioeconomic burden for societies. Undoubtedly, vaccines are the most efficient health care measure to prevent infections. Age-associated changes of the immune system are responsible for decreased immunogenicity and clinical efficacy of most currently used vaccines in older age. Efficacy of standard influenza vaccines is only 30-50% in the older population. Several approaches, such as higher antigen dose, use of MF59 as adjuvant and intradermal administration have been implemented in order to specifically target the aged immune system. The use of a 23-valent polysaccharide vaccine against Streptococcus pneumoniae has been amended by a 13-valent conjugated pneumococcal vaccine originally developed for young children several years ago to overcome at least some of the limitations of the T cell-independent polysaccharide antigens, but still is only approximately 50% protective against pneumonia. A liveattenuated vaccine against herpes zoster, which has been available for several years, demonstrated efficacy of 51% against herpes zoster and 67% against post-herpetic neuralgia. Protection was lower in the very old and decreased several years after vaccination. Recently, a recombinant vaccine containing the viral glycoprotein gE and the novel adjuvant AS01B has been licensed. Phase III studies demonstrated efficacy against herpes zoster of approx. 90% even in the oldest age groups after administration of two doses and many countries now recommend the preferential use of this vaccine. There are still many infectious diseases causing substantial morbidity in the older population, for which no vaccines are available so far. Extensive research is ongoing to develop vaccines against novel targets with several vaccine candidates already being clinically tested, which have the potential to substantially reduce health care costs and to save many lives. In addition to the development of novel and improved vaccines, which specifically target the aged immune system, it is also important to improve uptake of the existing vaccines in order to protect the vulnerable, older population.

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“… 30 , 33 , 34 Serotype replacement disease, next to expanding the coverage, has been one of the arguments for development of 10- and 13-valent conjugate vaccines. 41 – 43 These vaccines incorporate more of the most predominant serotypes, including the replacement serotypes ( Figure 2 ). 44 – 46 Also, after introduction of PCV13, serotype replacement continues.…”

Section: Pneumococcal Vaccines and Vaccinationmentioning

confidence: 99%

Triptych of the Hermit Saints: pneumococcal polysaccharide vaccines for the elderly

Rijkers

Yousif

Spoorenberg

et al. 2018

RMHP

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Pneumococcal pneumonia is a serious disease with considerable morbidity and mortality in the elderly. Despite adequate antibiotic treatment, the long-term mortality of pneumococcal pneumonia remains high. Preventive measures in the form of vaccination, therefore, are warranted. Twenty-three-valent polysaccharide vaccines have a broad coverage but limited efficacy. Pneumococcal conjugate vaccines have been shown in children to be able to prevent invasive and mucosal pneumococcal diseases. It should be realized that the serotype composition of current pneumococcal conjugate vaccines is not tailored for the elderly, and that replacement disease can occur. Yet, the current 13-valent conjugate vaccine has been shown to protect against infections with vaccine serotypes. Long-term mortality of pneumococcal pneumonia should be included in policy making about the introduction of these vaccines for the elderly.

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Pneumococcal Capsular Polysaccharide Immunity in the Elderly

Cited by 35 publications

References 114 publications

An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae

An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae

Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives

Triptych of the Hermit Saints: pneumococcal polysaccharide vaccines for the elderly

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