Comparison of the Immunogenicity and Safety of the Conventional Subunit, MF59-Adjuvanted, and Intradermal Influenza Vaccines in the Elderly

Seo, Yu Bin; Choi, Won Suk; Jacob, Louis; Song, Joon Young; Cheong, Hee Jin

doi:10.1128/cvi.00615-13

Cited by 35 publications

(36 citation statements)

References 23 publications

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“…The high-dose formulation of influenza vaccination is one example of an attempt to overcome reduced immune function through increased antigen dose. Alternative approaches may rely on the stimulation of specific immune responses; for example, the newly licensed MF59-adjuvanted influenza vaccine demonstrated to have higher immunogenicity and result in longer-lived antibody responses following vaccination (89–91). Additional examples include the use of GLA-SE (a TLR4 agonist) leading to increased production of TNFα, IL-6, and IL-12, as well as a Th1 shift in response to influenza challenge (92); or the use of Ov-ASP-1 (a helminth-derived protein adjuvant that stimulates both Th1 and Th2 responses with resulting increases in influenza-specific antibody titer in both young and old mice) (93).…”

Section: Resultsmentioning

confidence: 99%

Immunosenescence-Related Transcriptomic and Immunologic Changes in Older Individuals Following Influenza Vaccination

et al. 2016

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The goal of annual influenza vaccination is to reduce mortality and morbidity associated with this disease through the generation of protective immune responses. The objective of the current study was to examine markers of immunosenescence and identify immunosenescence-related differences in gene expression, gene regulation, cytokine secretion, and immunologic changes in an older study population receiving seasonal influenza A/H1N1 vaccination. Surprisingly, prior studies in this cohort revealed weak correlations between immunosenescence markers and humoral immune response to vaccination. In this report, we further examined the relationship of each immunosenescence marker (age, T cell receptor excision circle frequency, telomerase expression, percentage of CD28− CD4+ T cells, percentage of CD28− CD8+ T cells, and the CD4/CD8 T cell ratio) with additional markers of immune response (serum cytokine and chemokine expression) and measures of gene expression and/or regulation. Many of the immunosenescence markers indeed correlated with distinct sets of individual DNA methylation sites, miRNA expression levels, mRNA expression levels, serum cytokines, and leukocyte subsets. However, when the individual immunosenescence markers were grouped by pathways or functional terms, several shared biological functions were identified: antigen processing and presentation pathways, MAPK, mTOR, TCR, BCR, and calcium signaling pathways, as well as key cellular metabolic, proliferation and survival activities. Furthermore, the percent of CD4+ and/or CD8+ T cells lacking CD28 expression also correlated with miRNAs regulating clusters of genes known to be involved in viral infection. Integrated (DNA methylation, mRNA, miRNA, and protein levels) network biology analysis of immunosenescence-related pathways and genesets identified both known pathways (e.g., chemokine signaling, CTL, and NK cell activity), as well as a gene expression module not previously annotated with a known function. These results may improve our ability to predict immune responses to influenza and aid in new vaccine development, and highlight the need for additional studies to better define and characterize immunosenescence.

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Section: Resultsmentioning

confidence: 99%

Immunosenescence-Related Transcriptomic and Immunologic Changes in Older Individuals Following Influenza Vaccination

et al. 2016

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“…We will need to further explore the potency of this response to that of common adjuvants and with a mix of target antigens to fully assess the utility of Sbi-III-IV as a universal vaccine adjuvant. For instance, comparison of the action of Sbi-III-IV to the Glaxo-Smith-Kline’s adjuvant systems, particularly AS01 [58], or to MF59 [59] may be of key interest and recent approaches may provide ideal pre-clinical model systems to facilitate this [60, 61] before progression to clinical studies. The work is ongoing but the data herein demonstrate the initial proof of concept.…”

Section: Discussionmentioning

confidence: 99%

Utilisation of staphylococcal immune evasion protein Sbi as a novel vaccine adjuvant

Yang

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et al. 2018

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42Co--ligation of the B cell antigen receptor with complement receptor 2 on B--cells 43 via a C3d--opsonised antigen complex significantly lowers the threshold required 44 for B cell activation. Consequently, fusions of antigens with C3d polymers have 45 shown great potential in vaccine design. However, these linear arrays of C3d 46 multimers do not mimic the natural opsonisation of antigens with C3d. Here we 47 investigate the potential of using the unique complement activating 48 characteristics of Staphylococcal immune--evasion protein Sbi to develop a 49 pro--vaccine approach that spontaneously coats antigens with C3 degradation 50 products in a natural way. We show that Sbi rapidly triggers the alternative 51 complement pathway through recruitment of complement regulators, forming a 52 tripartite complex that acts as a competitive antagonist of factor H, resulting in 53 enhanced complement consumption. These functional results are corroborated 54 by the structure of this complement activating Sbi--III--IV:C3d:FHR--1 complex. 55Finally, we demonstrate that Sbi, fused with Mycobacterium tuberculosis antigen 56 Ag85b, causes efficient opsonisation with C3 fragments, thereby enhancing the 57 immune response significantly beyond that of Ag85b alone, providing proof of 58 concept for our pro--vaccine approach. 59 antigens by C3d at a molecular level and do not always enhance immune 82 responses [13]. After activation of C3, C3b attaches directly to the antigen 83 surface via the reactive thioester on the convex face of the protein's thioester 84 domain (TED). In the presence of complement regulators (factor I (FI) and its 85 co--factors, such as factor H (FH) and CR1) this is rapidly converted to iC3b and 86 then to C3d, exposing the concave CR2 binding site of the TED fragment away 87 from the antigen surface [14]. It is likely that multiple iC3b/C3d molecules attach 88 to complex antigens/pathogen surfaces during the initial activation phases of 89 complement, creating high--avidity binding site for complement fragment 90 receptors. 91In the last two decades, structural biology has helped to unveil many of the 92 molecular aspects that are crucial for the activation and regulation of the 93 complement system. Most notable are the crystal structures of the central 94 complement component activation states, native C3 [15], activated C3b and 95 inactive C3c [16]. The structure of C3b in complex with factors B and D [17] 96 subsequently revealed a detailed view of the alternative pathway C3 convertase 97 assembly and its activation, leading to the amplified cleavage of C3 molecules 98 that result in opsonisation and clearance of microbial pathogens and host debris. 99 The covalent attachment of C3b to surfaces does not discriminate between self 100 or non--self surfaces and requires tight regulation to protect host surfaces. 101 Structures of C3b in complex with FH domains 1--4 [18] and domains 19--20 [19, 102 20] provided insights into protection of host cells [21] and demonstrated how 103 5 factor H--related prote...

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“…The results showed that the PA adjuvant significantly increased the systemic and local antibody titers and the cellular immune response to the ITIV, particularly in the HPA-V group. The HPA-V group nearly fulfilled the immunogenicity evaluation criteria of the Committee for Medical Products for Human Use (seroprotection rate >60%, seroconversion rate >30%, and GMT fold >2) [1], with a seroconversion rate for the A/H3N2 antigen of 40% and fold increases in the HI GMTs for the A/H1N1 and A/H3N2 antigens of 4.04 and 5.90, respectively. Similarly, the mucosal antibody response and the total response were significantly improved in the HPA-V group, particularly for the A/H3N2 antigen.…”

Section: Discussionmentioning

confidence: 99%

“…Seasonal influenza is a common acute respiratory viral infection that causes annual epidemics with significant morbidity and mortality in high-risk populations [1–3]. Vaccine immunization against influenza is the most effective intervention.…”

Section: Introductionmentioning

confidence: 99%

Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59

et al. 2017

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Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA) has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV) via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI) methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs) for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

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Comparison of the Immunogenicity and Safety of the Conventional Subunit, MF59-Adjuvanted, and Intradermal Influenza Vaccines in the Elderly

Cited by 35 publications

References 23 publications

Immunosenescence-Related Transcriptomic and Immunologic Changes in Older Individuals Following Influenza Vaccination

Immunosenescence-Related Transcriptomic and Immunologic Changes in Older Individuals Following Influenza Vaccination

Utilisation of staphylococcal immune evasion protein Sbi as a novel vaccine adjuvant

Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59

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