A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal<i>Streptococcus pneumoniae</i>Challenge

Chan, Win-Yan; Entwisle, Claire; Ercoli, Giuseppe; Ramos‐Sevillano, Elisa; McIlgorm, Ann; Cecchini, Paola; Bailey, Christopher R.; Lam, Oliver; Whiting, Gail; Green, Nicola; Wheeler, Jun X.; Brown, Jeremy S.

doi:10.1128/iai.00846-18

Cited by 27 publications

(23 citation statements)

References 77 publications

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“…Multidimensional LC-MS/MS was carried out according the method described by Chan et al . 68 . The 12 fractions collected by high pH RP-HPLC separation were each subjected to 240-min LC-MS/MS peptide sequencing using a MS system (Thermo Scientific) equipped with a nano-electrospray ion source and two mass detectors, linear trap (LTQ) and Orbitrap, coupled with an Ultimate 3000 nano-LC system.…”

Section: Methodsmentioning

confidence: 99%

Immunogenicity profiling of protein antigens from capsular group B Neisseria meningitidis

Awanye

Chang

Wheeler

et al. 2019

Sci Rep

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Outer membrane vesicle (OMV)- based vaccines have been used to provide strain-specific protection against capsular group B Neisseria meningitidis infections, but the full breadth of the immune response against the components of the OMV has not been established. Sera from adults vaccinated with an OMV vaccine were used to screen 91 outer membrane proteins (OMPs) incorporated in an antigen microarray panel. Antigen-specific IgG levels were quantified pre-vaccination, and after 12 and 18 weeks. These results were compared with IgG levels from mice vaccinated with the same OMV vaccine. The repertoires of highly responding antigens in humans and mice overlapped, but were not identical. The highest responding antigens to human IgG comprised four integral OMPs (PorA, PorB, OpcA and PilQ), a protein which promotes the stability of PorA and PorB (RmpM) and two lipoproteins (BamC and GNA1162). These observations will assist in evaluating the role of minor antigen components within OMVs in providing protection against meningococcal infection. In addition, the relative dominance of responses to integral OMPs in humans emphasizes the importance of this subclass and points to the value of maintaining conformational epitopes from integral membrane proteins in vaccine formulations.

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Section: Methodsmentioning

confidence: 99%

Immunogenicity profiling of protein antigens from capsular group B Neisseria meningitidis

Awanye

Chang

Wheeler

et al. 2019

Sci Rep

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“…As recent work has illustrated differential efficacy of Prevnar vaccination in modulating the immune responses of adult mice to a post-influenza infection with a serotype 3 strain of Streptococcus pneumoniae, we chose to examine the impact of Pneumovax on these responses [30,40]. Given these findings, it would be plausible that other vaccines, designed with specific bacterial components, such as pneumococcal surface protein A (PspA) and pneumolysin (Ply) or liposomal encapsulation of polysaccharides (LEPS), may improve efficacy to post-influenza S. pneumoniae infection [31,[43][44][45]. Future work will need to evaluate if additional vaccine types can prove efficacious and further reduce inflammatory cytokine production while improving bacterial clearance post-influenza infection.…”

Section: Discussionmentioning

confidence: 99%

Impact of Influenza on Pneumococcal Vaccine Effectiveness during Streptococcus pneumoniae Infection in Aged Murine Lung

et al. 2020

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Changes in innate and adaptive immune responses caused by viral imprinting can have a significant direct or indirect influence on secondary infections and vaccine responses. The purpose of our current study was to investigate the role of immune imprinting by influenza on pneumococcal vaccine effectiveness during Streptococcus pneumoniae infection in the aged murine lung. Aged adult (18 months) mice were vaccinated with the pneumococcal polyvalent vaccine Pneumovax (5 mg/mouse). Fourteen days post vaccination, mice were instilled with PBS or influenza A/PR8/34 virus (3.5 × 102 PFU). Control and influenza-infected mice were instilled with PBS or S. pneumoniae (1 × 103 CFU, ATCC 6303) on day 7 of infection and antibacterial immune responses were assessed in the lung. Our results illustrate that, in response to a primary influenza infection, there was diminished bacterial clearance and heightened production of pro-inflammatory cytokines, such as IL6 and IL1β. Vaccination with Pneumovax decreased pro-inflammatory cytokine production by modulating NFҡB expression; however, these responses were significantly diminished after influenza infection. Taken together, the data in our current study illustrate that immune imprinting by influenza diminishes pneumococcal vaccine efficacy and, thereby, may contribute to increased susceptibility of older persons to a secondary infection with S. pneumoniae.

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“…In a Phase I clinical trial in healthy adults this vaccine elicited antibodies to a range of pneumococcal proteins including multiple conserved antigens, as well as T cell responses (172,173). Recently, a multiple-antigen pneumococcal vaccine, which utilizes TIGR4 whole cell lysates enriched for surface proteins by chromatography was shown to induce robust antibody response against several serotypes and protected mice against pneumonia (174).…”

Section: Future Perspectives To Improve Vaccination Of the Older Popumentioning

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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A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge

Cited by 27 publications

References 77 publications

Immunogenicity profiling of protein antigens from capsular group B Neisseria meningitidis

Immunogenicity profiling of protein antigens from capsular group B Neisseria meningitidis

Impact of Influenza on Pneumococcal Vaccine Effectiveness during Streptococcus pneumoniae Infection in Aged Murine Lung

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

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