Roles of Aluminum Hydroxide and Monophosphoryl Lipid A Adjuvants in Overcoming CD4+ T Cell Deficiency To Induce Isotype-Switched IgG Antibody Responses and Protection by T-Dependent Influenza Vaccine

Ko, Eunju; Lee, Young-Tae; Kim, Ki-Hye; Lee, Youri; Jung, Yu‐Jin; Kim, Min‐Chul; Lee, Yuna; Kang, Taeuk; Kang, Sang‐Moo

doi:10.4049/jimmunol.1600173

Cited by 39 publications

(31 citation statements)

References 39 publications

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“…The levels of these innate acute inflammatory cells appeared to be lower than those reported in previous studies on adjuvants such as oilin-water emulsion MF59 and combination AS04, alum C monophosphoryl lipid A (MPL, a TLR4 ligand). 41 These intrinsic differences between F VLP and F protein in generating inflammatory microenvironment might be contributing to developing differential quality of immunity responsible for enhancing or preventing RSV vaccine-associated disease.…”

Section: Discussionmentioning

confidence: 99%

Soluble F proteins exacerbate pulmonary histopathology after vaccination upon respiratory syncytial virus challenge but not when presented on virus-like particles

Lee

et al. 2017

Human Vaccines & Immunotherapeutics

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Respiratory syncytial virus (RSV) fusion (F) protein is suggested to be a protective vaccine target although its efficacy and safety concerns remain not well understood. We investigated immunogenicity, efficacy, and safety of F proteins in a soluble form or on virus-like particle (F-VLP). F VLP preferentially elicited IgG2a antibody and T helper type 1 (Th1) immune responses whereas F protein induced IgG1 isotype and Th2 responses. Despite lung viral clearance after prime or prime-boost and then RSV challenge, F protein immune mice displayed weight loss and lung histopathology and high mucus production and eosinophils. In contrast, prime or prime-boost vaccination of F VLP induced effective protection, prevented infiltration of eosinophils and vaccine- enhanced disease after challenge. This study provides insight into developing an effective and safe RSV vaccine candidate.

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Section: Discussionmentioning

confidence: 99%

Soluble F proteins exacerbate pulmonary histopathology after vaccination upon respiratory syncytial virus challenge but not when presented on virus-like particles

Lee

et al. 2017

Human Vaccines & Immunotherapeutics

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“…26 Both MF59 and AS04 adjuvanted influenza vaccinations were effective in inducing IgG isotype-switched antibodies and conferring protective immunity in a CD4 deficient mouse model. 13,27 MF59 was more potent than AS04 in exhibiting CD4independent adjuvant effects. AS04 showed a moderate level of CD4-dependency in inducing isotype-switched IgG antibodies, but AS04-adjuvanted T-dependent split influenza vaccine provided sufficient protection in CD4-deficient mice.…”

Section: Mf59 In Comparison With Other Adjuvantsmentioning

confidence: 87%

Immunology and efficacy of MF59-adjuvanted vaccines

Kang

2018

Human Vaccines & Immunotherapeutics

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Adjuvants are included in vaccine formulations to enhance the immunogenicity and efficacy of vaccines. MF59® is an oil-in-water emulsion adjuvant and licensed for use in pandemic and seasonal influenza vaccines in many countries. MF59 is safe and well tolerated in humans. MF59-adjuvanted vaccination spares vaccine dose and enhances hemagglutination inhibiting antibodies against homologous and heterologous influenza virus strains. The mechanisms of MF59 involve rapid induction of chemokines, inflammatory cytokines, recruiting multiple immune cells, uric acid and benign apoptosis of certain innate immune cells. The adjuvant effects of MF59 on generating vaccine-specific isotype-switched IgG antibodies, effector CD8 T cells, and protective immunity were retained even in a CD4-deficient condition by inducing effective immune-competent microenvironment with various innate and antigen presenting cells in a mouse model. CD4-independent adjuvant effects of MF59 might contribute to improving the vaccine efficacy in children, the elderly, and immunocompromised patients as well as in healthy adults. Further studies will be needed to broaden the use of MF59 in various vaccine antigens and populations as well as lead to better understanding of the action mechanisms of MF59 adjuvant.

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“…HI assay. Hemagglutination inhibition (HI) assay was performed as previously described (39). Immune sera were mixed with a receptor-destroying enzyme (Sigma-Aldrich, St. Louis, MO) and then incubated at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Complement C3 Plays a Key Role in Inducing Humoral and Cellular Immune Responses to Influenza Virus Strain-Specific Hemagglutinin-Based or Cross-Protective M2 Extracellular Domain-Based Vaccination

Kim

et al. 2018

J Virol

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The complement pathway is involved in eliminating antigen immune complexes. However, the role of the C3 complement system remains largely unknown in influenza virus M2 extracellular (M2e) domain or hemagglutinin (HA) vaccine-mediated protection after vaccination. Using a C3 knockout (C3 KO) mouse model, we found that complement protein C3 was required for effective induction of immune responses to vaccination with M2e-based or HA-based vaccines, which include isotype class-switched antibodies and effector CD4 and CD8 T cell responses. C3 KO mice after active immunization with cross-protective nonneutralizing M2e-based vaccine were not protected against influenza virus, although low levels of M2e-specific antibodies were protective after passive coadministration with virus in wild-type mice. In contrast, C3 KO mice that were immunized with strain-specific neutralizing HA-based vaccine were protected against homologous virus challenge despite lower levels of HA antibody responses. C3 KO mice showed impaired maintenance of innate immune cells and a defect in innate immune responses upon exposure to antigens. The findings in this study suggest that C3 is required for effective induction of humoral and cellular adaptive immune responses as well as protective immunity after nonneutralizing influenza M2e vaccination. Complement is the well-known innate immune defense system involved in the opsonization and lysis of pathogens but is less studied in establishing adaptive immunity after vaccination. Influenza virus HA-based vaccination confers protection via strain-specific neutralizing antibodies, whereas M2e-based vaccination induces a broad spectrum of protection by immunity against the conserved M2e epitopes. This study revealed the critical roles of C3 complement in inducing humoral and cellular immune responses after immunization with M2e or HA vaccines. C3 was found to be required for protection by M2e-based but not by HA-based active vaccination as well as for maintaining innate antigen-presenting cells. Findings in this study have insight into better understanding the roles of C3 complement in inducing effective innate and adaptive immunity as well as in conferring protection by cross-protective conserved M2e vaccination.

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Roles of Aluminum Hydroxide and Monophosphoryl Lipid A Adjuvants in Overcoming CD4+ T Cell Deficiency To Induce Isotype-Switched IgG Antibody Responses and Protection by T-Dependent Influenza Vaccine

Cited by 39 publications

References 39 publications

Soluble F proteins exacerbate pulmonary histopathology after vaccination upon respiratory syncytial virus challenge but not when presented on virus-like particles

Soluble F proteins exacerbate pulmonary histopathology after vaccination upon respiratory syncytial virus challenge but not when presented on virus-like particles

Immunology and efficacy of MF59-adjuvanted vaccines

Complement C3 Plays a Key Role in Inducing Humoral and Cellular Immune Responses to Influenza Virus Strain-Specific Hemagglutinin-Based or Cross-Protective M2 Extracellular Domain-Based Vaccination

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