scholarly journals Cholesteryl Pullulan Encapsulated TNF-αNanoparticles Are an Effective Mucosal Vaccine Adjuvant against Influenza Virus

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Daiki Nagatomo ◽  
Madoka Taniai ◽  
Harumi Ariyasu ◽  
Mutsuko Taniguchi ◽  
Miho Aga ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Virus Infection ◽  
Repeated Administration ◽  
Mucosal Vaccine ◽  
Nasal Administration ◽  
Vaccine Adjuvant ◽  
Severe Toxicity ◽  
Lethal Challenge ◽  
Antigen Uptake ◽  
Humoral And Cellular Immunity

We encapsulated tumor necrosis factor-α(TNF-α), a major proinflammatory cytokine, into cholesteryl pullulan (CHP) to prepare TNF/CHP nanoparticles. In this report, we describe the immune-enhancing capability of the nanoparticles to act as a vaccine adjuvant. TNF/CHP nanoparticles showed excellent storage stability and enhanced host immune responses to external immunogens. The nanoparticles were effective via the nasal route of administration for inducing systemic IgG1as well as mucosal IgA. We applied the nanoparticles in a model experimental influenza virus infection to investigate their adjuvant ability. TNF/CHP nanoparticles combined with a conventional split vaccine protected mice via nasal administration against a lethal challenge of A/PR/8/34 (H1N1) influenza virus. Mechanistic studies showed that the nanoparticles enhanced antigen uptake by dendritic cells (DCs) and moderately induced the expression of inflammation-related genes in nasopharynx lymphoid tissue (NALT), leading to the activation of both B and T cells. Preliminary safety study revealed no severe toxicity to TNF/CHP nanoparticles. Slight-to-moderate influences in nasal mucosa were observed only in the repeated administration and they seemed to be reversible. Our data show that TNF/CHP nanoparticles effectively enhance both humoral and cellular immunity and could be a potential adjuvant for vaccines against infectious diseases, especially in the mucosa.

scholarly journals Chimeric Hemagglutinin-Based Live-Attenuated Vaccines Confer Durable Protective Immunity against Influenza A Viruses in a Preclinical Ferret Model

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 40
Author(s):  
Wen-Chun Liu ◽  
Raffael Nachbagauer ◽  
Daniel Stadlbauer ◽  
Shirin Strohmeier ◽  
Alicia Solórzano ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Virus Vaccine ◽  
Antibody Responses ◽  
Upper Respiratory Tract ◽  
Influenza A Viruses ◽  
Humoral And Cellular Immunity ◽  
Stalk Domain ◽  
One Year

Epidemic or pandemic influenza can annually cause significant morbidity and mortality in humans. We developed novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccines, which contain a conserved HA stalk domain from a 2009 pandemic H1N1 (pH1N1) strain combined with globular head domains from avian influenza A viruses. Our previous reports demonstrated that prime-boost sequential immunizations induced robust antibody responses directed toward the conserved HA stalk domain in ferrets. Herein, we further followed vaccinated animals for one year to compare the efficacy and durability of these vaccines in the preclinical ferret model of influenza. Although all cHA-based immunization regimens induced durable HA stalk-specific and heterosubtypic antibody responses in ferrets, sequential immunization with live-attenuated influenza virus vaccines (LAIV-LAIV) conferred the best protection against upper respiratory tract infection by a pH1N1 influenza A virus. The findings from this study suggest that our sequential immunization strategy for a cHA-based universal influenza virus vaccine provides durable protective humoral and cellular immunity against influenza virus infection.

scholarly journals Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus

2010 ◽  
Vol 84 (24) ◽  
pp. 12703-12712 ◽  
Author(s):  
Hiroyuki Kayamuro ◽  
Yasuo Yoshioka ◽  
Yasuhiro Abe ◽  
Shuhei Arita ◽  
Kazufumi Katayama ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Interleukin 1 ◽  
Influenza Virus Infection ◽  
Mucosal Vaccine ◽  
Vaccine Adjuvants ◽  
Mucosal Surfaces ◽  
Mucosal Vaccines ◽  
Etiological Agents ◽  
Family Cytokine

ABSTRACT A safe and potent adjuvant is needed for development of mucosal vaccines against etiological agents, such as influenza virus, that enter the host at mucosal surfaces. Cytokines are potential adjuvants for mucosal vaccines because they can enhance primary and memory immune responses enough to protect against some infectious agents. For this study, we tested 26 interleukin (IL) cytokines as mucosal vaccine adjuvants and compared their abilities to induce antigen (Ag)-specific immune responses against influenza virus. In mice intranasally immunized with recombinant influenza virus hemagglutinin (rHA) plus one of the IL cytokines, IL-1 family cytokines (i.e., IL-1α, IL-1β, IL-18, and IL-33) were found to increase Ag-specific immunoglobulin G (IgG) in plasma and IgA in mucosal secretions compared to those after immunization with rHA alone. In addition, high levels of both Th1- and Th2-type cytokines were observed in mice immunized with rHA plus an IL-1 family cytokine. Furthermore, mice intranasally immunized with rHA plus an IL-1 family cytokine had significant protection against a lethal influenza virus infection. Interestingly, the adjuvant effects of IL-18 and IL-33 were significantly decreased in mast cell-deficient W/W v mice, indicating that mast cells have an important role in induction of Ag-specific mucosal immune responses induced by IL-1 family cytokines. In summary, our results demonstrate that IL-1 family cytokines are potential mucosal vaccine adjuvants and can induce Ag-specific immune responses for protection against pathogens like influenza virus.

scholarly journals MyD88 Signaling Is Indispensable for Primary Influenza A Virus Infection but Dispensable for Secondary Infection

2010 ◽  
Vol 84 (24) ◽  
pp. 12713-12722 ◽  
Author(s):  
Sang-Uk Seo ◽  
Hyung-Joon Kwon ◽  
Joo-Hye Song ◽  
Young-Ho Byun ◽  
Baik Lin Seong ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Protective Efficacy ◽  
Secondary Infection ◽  
Influenza Virus Infection ◽  
Lethal Challenge ◽  
Influenza A Virus Infection ◽  
Myd88 Signaling ◽  
Deficient Mice

ABSTRACT Recent studies have revealed that innate immunity is involved in the development of adaptive immune responses; however, its role in protection is not clear. In order to elucidate the exact role of Toll-like receptor (TLR) or RIG-I-like receptor (RLR) signaling on immunogenicity and protective efficacy against influenza A virus infection (A/PR/8/34 [PR8]; H1N1), we adapted several innate signal-deficient mice (e.g., TRIF−/−, MyD88−/−, MyD88−/− TRIF−/−, TLR3−/− TLR7−/−, and IPS-1−/−). In this study, we found that MyD88 signaling was required for recruitment of CD11b+ granulocytes, production of early inflammatory cytokines, optimal proliferation of CD4 T cells, and production of Th1 cytokines by T cells. However, PR8 virus-specific IgG and IgA antibody levels in both systemic and mucosal compartments were normal in TLR- and RLR-deficient mice. To further assess the susceptibility of these mice to influenza virus infection, protective efficacy was determined after primary or secondary lethal challenge. We found that MyD88−/− and MyD88−/− TRIF−/− mice were more susceptible to primary influenza virus infection than the B6 mice but were fully protected against homologous (H1N1) and heterosubtypic (H5N2) secondary infection when primed with a nonlethal dose of PR8 virus. Taken together, these results show that MyD88 signaling plays an important role for resisting primary influenza virus infection but is dispensable for protection against a secondary lethal challenge.

scholarly journals Synthetic Double-Stranded RNA Poly(I:C) Combined with Mucosal Vaccine Protects against Influenza Virus Infection

2005 ◽  
Vol 79 (5) ◽  
pp. 2910-2919 ◽  
Author(s):  
Takeshi Ichinohe ◽  
Izumi Watanabe ◽  
Satoshi Ito ◽  
Hideki Fujii ◽  
Masami Moriyama ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Protective Effect ◽  
Intranasal Administration ◽  
Influenza Virus Infection ◽  
Mucosal Vaccine ◽  
Poly I:C ◽  
Intracerebral Injection ◽  
Mrna Levels ◽  
H1n1 Vaccine ◽  
Double Stranded Rna

ABSTRACT The mucosal adjuvant effect of synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid [poly(I:C)] against influenza virus was examined under intranasal coadministration with inactivated hemagglutinin (HA) vaccine in BALB/c mice and was shown to have a protective effect against both nasal-restricted infection and lethal lung infection. Intranasal administration of vaccine from PR8 (H1N1) with poly(I:C) induced a high anti-HA immunoglobulin A (IgA) response in the nasal wash and IgG antibody response in the serum, while vaccination without poly(I:C) induced little response. Intracerebral injection confirmed the safety of poly(I:C). In addition, we demonstrated that administration of poly(I:C) with either A/Beijing (H1N1) or A/Yamagata (H1N1) vaccine conferred complete protection against PR8 challenge in this mouse nasal infection model, suggesting that poly(I:C) possessed cross-protection ability against variant viruses. To investigate the mechanism of the protective effect of poly(I:C), mRNA levels of Toll-like receptors and cytokines were examined in the nasal-associated lymphoid tissue after vaccination or virus challenge. Intranasal administration of HA vaccine with poly(I:C) up-regulated expression of Toll-like receptor 3 and alpha/beta interferons as well as Th1- and Th2-related cytokines. We propose that poly(I:C) is a new effective intranasal adjuvant for influenza virus vaccine.

scholarly journals Cross-Protection of Chicken Immunoglobulin Y Antibodies against H5N1 and H1N1 Viruses Passively Administered in Mice

2011 ◽  
Vol 18 (7) ◽  
pp. 1083-1090 ◽  
Author(s):  
Michael G. Wallach ◽  
Richard J. Webby ◽  
Fakhrul Islam ◽  
Stephen Walkden-Brown ◽  
Eva Emmoth ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Pandemic ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Virus Infectivity ◽  
Lethal Challenge ◽  
H5n1 Influenza

ABSTRACTInfluenza viruses remain a major threat to global health due to their ability to undergo change through antigenic drift and antigenic shift. We postulated that avian IgY antibodies represent a low-cost, effective, and well-tolerated approach that can easily be scaled up to produce enormous quantities of protective antibodies. These IgY antibodies can be administered passively in humans (orally and intranasally) and can be used quickly and safely to help in the fight against an influenza pandemic. In this study, we raised IgY antibodies against H1N1, H3N2, and H5N1 influenza viruses. We demonstrated that, using whole inactivated viruses alone and in combination to immunize hens, we were able to induce a high level of anti-influenza virus IgY in the sera and eggs, which lasted for at least 2 months after two immunizations. Furthermore, we found that by use ofin vitroassays to test for the ability of IgY to inhibit hemagglutination (HI test) and virus infectivity (serum neutralization test), IgYs inhibited the homologous as well as in some cases heterologous clades and strains of viruses. Using anin vivomouse model system, we found that, when administered intranasally 1 h prior to infection, IgY to H5N1 protected 100% of the mice against lethal challenge with H5N1. Of particular interest was the finding that IgY to H5N1 cross-protected against A/Puerto Rico/8/34 (H1N1) bothin vitroandin vivo. Based on our results, we conclude that anti-influenza virus IgY can be used to help prevent influenza virus infection.

scholarly journals Virus-specific interferon action. Protection of newborn Mx carriers against lethal infection with influenza virus.

1981 ◽  
Vol 154 (1) ◽  
pp. 199-203 ◽  
Author(s):  
O Haller ◽  
H Arnheiter ◽  
I Gresser ◽  
J Lindenmann
Keyword(s):  
Influenza Virus ◽  
Influenza Virus Infection ◽  
Specific Effect ◽  
Influenza Viruses ◽  
Encephalomyocarditis Virus ◽  
Lethal Challenge ◽  
Newborn Mice ◽  
Adult Mice ◽  
High Degree

The efficacy of interferon in antiviral protection of newborn mice differing at the Mx locus was investigated. Adult mice bearing the allele Mx exhibit a high degree of specific resistance toward lethal challenge with influenza viruses. In contrast, newborn Mx carriers are virtually as susceptible to influenza viruses as newborn mice devoid of Mx. Resistance can be abrogated by treating adult animals with anti-interferon serum. Here, we provide direct evidence of a virus-specific effect of interferon in vivo: newborn mice carrying the resistance gene Mx could be protected against lethal influenza virus infection with doses of interferon that were not protective in the absence of Mx. The efficacy of interferon towards a picornavirus (encephalomyocarditis virus) and a rhabdovirus (vesicular stomatitis virus) was independent of Mx.

scholarly journals The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Steven M Blaauboer ◽  
Samira Mansouri ◽  
Heidi R Tucker ◽  
Hatti L Wang ◽  
Vincent D Gabrielle ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Cyclic Gmp ◽  
Mucosal Vaccine ◽  
Vaccine Adjuvant ◽  
Vaccine Response ◽  
Antigen Uptake ◽  
Mucosal Adjuvant ◽  
Adjuvanted Vaccine

Effective mucosal adjuvants enhance the magnitude and quality of the vaccine response. Cyclic di-GMP (CDG) is a promising mucosal vaccine adjuvant. However, its in vivo mechanisms are unclear. Here, we showed, in mice, that CDG elicits stronger Ab and TH responses than the mammalian 2′3′-cyclic GMP-AMP (cGAMP), and generated better protection against Streptococcus pneumoniae infection than 2′3′-cGAMP adjuvanted vaccine. We identified two in vivo mechanisms of CDG. First, intranasally administered CDG greatly enhances Ag uptake, including pinocytosis and receptor-mediated endocytosis in vivo. The enhancement depends on MPYS (STING, MITA) expression in CD11C+ cells. Second, we found that CDG selectively activated pinocytosis-efficient-DCs, leading to TH polarizing cytokines IL-12p70, IFNγ, IL-5, IL-13, IL-23, and IL-6 production in vivo. Notably, CDG induces IFNλ, but not IFNβ, in vivo. Our study revealed previously unrecognized in vivo functions of MPYS and advanced our understanding of CDG as a mucosal vaccine adjuvant.

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