Progress in mucosal immunization for protection against pneumococcal pneumonia

Gonçalves, Viviane Maimoni; Kaneko, Kan; Solórzano, Carla; MacLoughlin, Ronan; Saleem, Imran; Miyaji, Eliane N.

doi:10.1080/14760584.2019.1643719

Cited by 8 publications

(7 citation statements)

References 122 publications

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“…The Alum adjuvant, used here, helps to maintain higher circulating levels of antibodies for a longer time in relation to an antigen inoculated only in aqueous solution (Jafari et al, 2017). Good results obtained with the antigens alone may be an indication that they will be even better when formulated with novel delivery technologies such as nanoparticles, nanogels and bacterial or viral-like particles (BLPs and VLPs, respectively), generating robust humoral and cellular responses (Gonçalves et al, 2019). Some protein vaccines developed against pneumococcus have successfully undergone phase 1 and 2 clinical trials, however, no vaccine other than capsular polysaccharide-based, whether conjugated (PCV) or not, has been in a phase 3 and licensed (Oliveira et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Conserved protein-based vaccines have been proposed as alternatives to currently available vaccines ( Briles et al, 2000a ; Miyaji et al, 2013 ; Gonçalves et al, 2019 ), which may solve aforementioned issues and still be able to protect risk groups and adult population from pneumococcal diseases. Pneumococcal surface protein A (PspA) is an important virulence factor ( Senkovich et al, 2007 ) and the protein is present in most clinical isolates of S. pneumoniae ( Ren et al, 2012 ; Khan and January 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Peptide linker increased the stability of pneumococcal fusion protein vaccine candidate

Zane

Kraschowetz

Trentini

et al. 2023

Front. Bioeng. Biotechnol.

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Streptococcus pneumoniae is a bacterial pathogen exclusive to humans, responsible for respiratory and systemic diseases. Pneumococcal protein vaccines have been proposed as serotype-independent alternatives to currently used conjugated polysaccharide vaccines, which have presented limitations regarding their coverage. Previously in our group, pneumococcal surface protein A (PspA) and detoxified pneumolysin (PdT) were genetically fused and the hybrid protein protected mice against pneumococcal challenge, offered higher cross-protection against different strains and showed greater opsonophagocytosis rate than co-administered proteins. As juxtaposed fusion was unstable to upscale production of the protein, flexible (PspA-FL-PdT) and rigid (PspA-RL-PdT) molecular linkers were inserted between the antigens to increase stability. This work aimed to produce recombinant fusion proteins, evaluate their stability after linker insertion, both in silico and experimentally, and enable the production of two antigens in a single process. The two constructs with linkers were cloned into Escherichia coli and hybrid proteins were purified using chromatography; purity was evaluated by SDS-PAGE and stability by Western blot and high performance size exclusion chromatography. PspA-FL-PdT showed higher stability at −20°C and 4°C, without additional preservatives. In silico analyses also showed differences regarding stability of the fusion proteins, with molecule without linker presenting disallowed amino acid positions in Ramachandran plot and PspA-FL-PdT showing the best scores, in agreement with experimental results. Mice were immunized with three doses and different amounts of each protein. Both fusion proteins protected all groups of mice against intranasal lethal challenge. The results show the importance of hybrid protein structure on the stability of the products, which is essential for a successful bioprocess development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Peptide linker increased the stability of pneumococcal fusion protein vaccine candidate

Zane

Kraschowetz

Trentini

et al. 2023

Front. Bioeng. Biotechnol.

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“…No data on immunogenicity in humans is available so far. A comprehensive review of mucosal pneumococcal vaccine candidates has recently been published (194).…”

Section: Induction Of Secretory Iga Antibodies and Mucosal Deliverymentioning

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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“…Importantly, in humans, experimental pneumococcal carriage, where live pneumococci are administered intranasally to volunteers, similarly elicited systemic antibody responses [127,128], elicited lung IL-17 + CD4 + memory T cells [129], stimulated tissue resident innate immune cells [130], and protected against re-colonization by the same serotype [131]. Further, intranasal delivery of pneumococcal protein-based vaccines along with adjuvants protected against invasive disease in mouse models [132]. Thus, intranasal immunizations that trigger systemic and mucosal immune responses are likely viable strategies to elicit host protection against lung infections.…”

Section: Intranasal Vaccine Delivery For Pneumococcal Diseasementioning

confidence: 99%

Intranasal Vaccine Delivery Technology for Respiratory Tract Disease Application with a Special Emphasis on Pneumococcal Disease

et al. 2021

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This mini-review will cover recent trends in intranasal (IN) vaccine delivery as it relates to applications for respiratory tract diseases. The logic and rationale for IN vaccine delivery will be compared to methods and applications accompanying this particular administration route. In addition, we will focus extended discussion on the potential role of IN vaccination in the context of respiratory tract diseases, with a special emphasis on pneumococcal disease. Here, elements of this disease, including its prevalence and impact upon the elderly population, will be viewed from the standpoint of improving health outcomes through vaccine design and delivery technology and how IN administration can play a role in such efforts.

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Progress in mucosal immunization for protection against pneumococcal pneumonia

Abstract: The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription.

Cited by 8 publications

References 122 publications

Peptide linker increased the stability of pneumococcal fusion protein vaccine candidate

Peptide linker increased the stability of pneumococcal fusion protein vaccine candidate

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

Intranasal Vaccine Delivery Technology for Respiratory Tract Disease Application with a Special Emphasis on Pneumococcal Disease

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