MF59 Mediates Its B Cell Adjuvanticity by Promoting T Follicular Helper Cells and Thus Germinal Center Responses in Adult and Early Life

Gavillet, Beatris Mastelic; Eberhardt, Christiane S.; Auderset, Floriane; Castellino, Flora; Seubert, Anja; Tregoning, John S.; Lambert, Paul‐Henri; Gregorio, Ennio De; Giudice, Giuseppe Del; Siegrist, Claire‐Anne

doi:10.4049/jimmunol.1402071

Cited by 109 publications

(67 citation statements)

References 56 publications

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“…We recently demonstrated that MF59 is highly effective in juvenile (3-week-old) animals, and MF59 has also been shown to improve immunogenicity in children over 6 months old (30), but it had limited efficacy in 1-week-old mice and has not been tested in younger infants. In the current study, we demonstrated that NanoSiO2 was effective in early life, leading to a significant reduction in disease following infection compared to the results seen with antigen alone.…”

Section: Discussionmentioning

confidence: 99%

Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice

Russell

McDonald

Lambert

et al. 2016

J Virol

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Neonates are at a high risk of infection, but vaccines are less effective in this age group; tailored adjuvants could potentially improve vaccine efficacy. Increased understanding about danger sensing by the innate immune system has led to the rational design of novel adjuvants. But differences in the neonatal innate immune response, for example, to Toll-like receptor (TLR) agonists, can reduce the efficacy of these adjuvants in early life. We therefore targeted alternative danger-sensing pathways, focusing on a range of compounds described as inflammasome agonists, including nanoscale silicon dioxide (NanoSiO2), calcium pyrophosphate dihydrate (CPPD) crystals, and muramyl tripeptide (M-Tri-DAP), for their ability to act as adjuvants. In vitro, these compounds induced an interleukin 1-beta (IL-1␤) response in the macrophage-like cell line THP1. In vivo, adult CB6F1 female mice were immunized intramuscularly with H1N1 influenza vaccine antigens in combination with NanoSiO2, CPPD, or M-Tri-DAP and subsequently challenged with H1N1 influenza virus (A/England/195/2009). The adjuvants boosted anti-hemagglutinin IgG and IgA antibody levels. Both adult and neonatal animals that received NanoSiO2-adjuvanted vaccines lost significantly less weight and recovered earlier after infection than control animals treated with antigen alone. Administration of the adjuvants led to an influx of activated inflammatory cells into the muscle but to little systemic inflammation measured by serum cytokine levels. Blocking IL-1␤ or caspase 1 in vivo had little effect on NanoSiO2 adjuvant function, suggesting that it may work through pathways other than the inflammasome. Here we demonstrate that NanoSiO2 can act as an adjuvant and is effective in early life. IMPORTANCEVaccines can fail to protect the most at-risk populations, including the very young, the elderly, and the immunocompromised. There is a gap in neonatal immunity between the waning of maternal protection and routine infant immunization schedules, exacerbated by the failure of vaccines to work in the first months of life. One approach is to design age-specific formulations, with more-effective adjuvants, based on our understanding of the nature of the neonatal immune response. We chose to target the inflammasome, a molecular complex capable of detecting infection and cell damage and of triggering IL-1␤-driven inflammation. We screened a range of compounds in vitro and in vivo and identified three lead candidates: NanoSiO2, CPPD, and MTri-DAP. Of these, NanoSiO2 was the most effective and boosted the anti-influenza virus response in both adult and neonatal mice. This finding is important for the development of age-specific vaccines, designed using our knowledge of the neonatal immune response. Infants bear the brunt of mortality and morbidity from infectious diseases, with 36% of the annual 3.3 million deaths in newborn children caused by infections (1). Influenza virus infection is especially prevalent in early life, with high rates of hospitalization (50 to 100 cases ...

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Section: Discussionmentioning

confidence: 99%

Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice

Russell

McDonald

Lambert

et al. 2016

J Virol

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“…The earliest and most abundantly recruited cell type is neutrophils, followed by monocytes, eosinophils and later dendritic cells (DCs) and macrophages. After the recruitment of immune cells into the injection site, MF59 can accelerate and enhance monocyte differentiation into DCs, augment antigen uptake, and facilitate migration of DCs into tissue-draining lymph nodes to prime adaptive immune responses [37-39]. The combination of MF59 adjuvant dramatically improved immunogenicity of the vaccine.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice

Deng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. Methods: Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. Results: The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. Conclusions: The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence.

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“…Squalene emulsified with surfactants serves as an adjuvant (MF59 and AS03) that drives robust antibody responses, polyfunctional TH1 cells and TFH cells, and enhanced immunity to heterotypic strains of influenza [77–82]. Uniquely, antibody isotype switching is induced by MF59 in the absence of CD4 + T cells, however apparently the plasma cells making this antibody don’t live for a long time in the absence of T cell help [83].…”

Section: Emulsion Based Adjuvantsmentioning

confidence: 99%

Old and new adjuvants

McKee

Marrack

2017

Current Opinion in Immunology

172

122

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MF59 Mediates Its B Cell Adjuvanticity by Promoting T Follicular Helper Cells and Thus Germinal Center Responses in Adult and Early Life

Cited by 109 publications

References 56 publications

Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice

Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice

The Protective Effects of the A/ZJU01/ PR8/2013 Split H7N9 Avian Influenza Vaccine Against Highly Pathogenic H7N9 in BALB/c Mice

Old and new adjuvants

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