Heterosubtypic Immunity against Human Influenza A Viruses, Including Recently Emerged Avian H5 and H9 Viruses, Induced by FLU–ISCOM Vaccine in Mice Requires both Cytotoxic T-Lymphocyte and Macrophage Function

Sambhara, Suryaprakash; Kurichh, Anjna; Miranda, Renata Lima de; Tumpey, Terrence M.; Rowe, Thomas; Renshaw, Mary; Arpino, Rita; Tamane, Alan; Kandil, Ali A.; James, Olive; Underdown, Brian J.; Klein, Michel; Katz, Jacqueline M.; Burt, David S.

doi:10.1006/cimm.2001.1835

Cited by 123 publications

(92 citation statements)

References 31 publications

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“…In animal models, heterosubtypic cross‐protection against challenge with highly pathogenic H5N1 virus has been observed with influenza vaccines using mucosal adjuvants or immunostimulating complexes 21 , 52 . These data support the view that induction of cross‐reactive antibodies in humans is clinically relevant.…”

Section: Confronting Pandemic Influenzasupporting

confidence: 57%

MF59^®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

Banzhoff

Pellegrini

Giudice

et al. 2008

Influenza Resp Viruses

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Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross‐reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non‐adjuvanted pre‐pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre‐pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross‐reactive immunogenicity. MF59®, the first oil‐in‐water emulsion licensed as an adjuvant for human use, can enhance vaccine immune responses through multiple mechanisms. A trivalent MF59‐adjuvanted seasonal influenza vaccine (Fluad®) has shown to induce significantly higher immune responses to influenza vaccination in the elderly, compared with non‐adjuvanted vaccines, and to provide cross‐reactive immunity against divergent influenza strains. Similar results have been generated with a MF59‐adjuvanted H5N1 pre‐pandemic vaccine, which showed higher and broader immunogenicity compared with non‐adjuvanted pre‐pandemic vaccines.

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Section: Confronting Pandemic Influenzasupporting

confidence: 57%

MF59^®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

Banzhoff

Pellegrini

Giudice

et al. 2008

Influenza Resp Viruses

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“…In contrast, M2 VLP supplemented vaccination induced strong cross-reactive binding antibodies to virions of different subtypes. Nonneutralizing anti-influenza humoral immunity was shown to confer protection (17,18) and to be dependent on opsonophagocytosis of influenza virions by macrophages (15). It was recently reported that monoclonal antibodies binding to multimeric M2 peptides were more protective than antibodies binding to monomeric M2 peptide (19).…”

Section: Discussionmentioning

confidence: 99%

“…DCs and macrophage cells might play a role in mediating cross-protection provided by nonneutralizing antibodies. It was previously reported that macrophages were involved in presenting cross-protective effects observed in vitro by nonneutralizing antibodies to influenza antigens (18). DC/macrophage cells that take up clodronate through liposome vesicles are depleted by apoptosis (21).…”

Section: Discussionmentioning

confidence: 99%

Vaccination inducing broad and improved cross protection against multiple subtypes of influenza A virus

Song

Rooijen

Bozja³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

137

120

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Development of an influenza vaccine that provides broadly cross-protective immunity has been a scientific challenge for more than half a century. This study presents an approach to overcome strain-specific protection by supplementing conventional vaccines with virus-like particles (VLPs) containing the conserved M2 protein (M2 VLPs) in the absence of adjuvants. We demonstrate that an inactivated influenza vaccine supplemented with M2 VLPs prevents disease symptoms without showing weight loss and confers complete cross protection against lethal challenge with heterologous influenza A viruses including the 2009 H1N1 pandemic virus as well as heterosubtypic H3N2 and H5N1 influenza viruses. Cross-protective immunity was long-lived, for more than 7 mo. Immune sera from mice immunized with M2 VLP supplemented vaccine transferred cross protection to naive mice. Dendritic and macrophage cells were found to be important for this cross protection mediated by immune sera. The results provide evidence that supplementation of seasonal influenza vaccines with M2 VLPs is a promising approach for overcoming the limitation of strain-specific protection by current vaccines and developing a universal influenza A vaccine.

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“…Several approaches have been proposed for the delivery of Ags and drugs to the cytosol, such as cell-penetrating peptides that carry their cargo across the plasma membrane (2, 3), pH-sensitive and fusogenic liposomes that break up phagosomes (4-6), micellebased immune-stimulating complexes that may facilitate Ag cross-presentation (7,8), and recombinantly modified viruses (9)(10)(11) and bacteria (12)(13)(14)(15) that trigger CTLs. Also, microparticles or nanoparticles made from biodegradable polymers, such as poly (lactide-co-glycolide) (PLGA), have been investigated for the cytosolic delivery of vaccines.…”

Section: T He Cd8 Ctls Play a Central Role In Fighting Diseasesmentioning

confidence: 99%

Photosensitizer and Light Pave the Way for Cytosolic Targeting and Generation of Cytosolic CD8 T Cells Using PLGA Vaccine Particles

Bruno

Waeckerle-Men

Håkerud

et al. 2015

The Journal of Immunology

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The generation of CTLs is crucial in the immunological fight against cancer and many infectious diseases. To achieve this, vaccine Ags need to be targeted to the cytosol of dendritic cells, which can activate CD8 T cells via MHC class I (MHCI). Therefore, such targeting has become one of the major objectives of vaccine research. In this study, we aimed to bypass the unwanted and default MHC class II Ag presentation and trigger MHCI presentation by using a photosensitizer that, upon light activation, would facilitate cytosolic targeting of codelivered Ag. Poly(lactide-co-glycolide) microparticles ∼1 μm size were loaded with OVA and the photosensitizer tetraphenyl chlorine disulphonate (TPCS2a) and administered intradermally in mice, which were illuminated 1 d later for activation of the photosensitizer. Immunization in the presence of TPCS2a significantly increased activation of CD8 T cells compared with immunization without TPCS2a and as measured by CD8 T cell proliferation, production of proinflammatory IFN-γ, TNF-α, and IL-2, and prevention of tumor growth. Cytotoxicity was demonstrated by granzyme B production in vitro and by in vivo killing of CFSE-labeled targets. CD4-dependent Ab responses were abrogated in mice immunized with TPCS2a-containing particles, suggesting that photosensitization facilitated a shift from default MHC class II toward MHCI Ag presentation. Hence, vaccine particles with Ag and photosensitizers proved an effective vehicle or adjuvant for stimulation of CTLs, and they may find potential application in therapeutic cancer vaccination and in prophylactic and therapeutic vaccination against intracellular infections.

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Heterosubtypic Immunity against Human Influenza A Viruses, Including Recently Emerged Avian H5 and H9 Viruses, Induced by FLU–ISCOM Vaccine in Mice Requires both Cytotoxic T-Lymphocyte and Macrophage Function

Cited by 123 publications

References 31 publications

MF59^®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

MF59^®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

Vaccination inducing broad and improved cross protection against multiple subtypes of influenza A virus

Photosensitizer and Light Pave the Way for Cytosolic Targeting and Generation of Cytosolic CD8 T Cells Using PLGA Vaccine Particles

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Heterosubtypic Immunity against Human Influenza A Viruses, Including Recently Emerged Avian H5 and H9 Viruses, Induced by FLU–ISCOM Vaccine in Mice Requires both Cytotoxic T-Lymphocyte and Macrophage Function

Cited by 123 publications

References 31 publications

MF59®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

MF59®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

Vaccination inducing broad and improved cross protection against multiple subtypes of influenza A virus

Photosensitizer and Light Pave the Way for Cytosolic Targeting and Generation of Cytosolic CD8 T Cells Using PLGA Vaccine Particles

Contact Info

Product

Resources

About

MF59^®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

MF59^®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis