A formulated poly (I:C)/CCL21 as an effective mucosal adjuvant for gamma-irradiated influenza vaccine

Abstract Background Several studies on gamma-irradiated influenza A virus (γ-Flu) have revealed its superior efficacy for inducing homologous and heterologous virus-specific immunity. However, many inactivated vaccines, notably in nasal delivery, require adjuvants to increase the quality and magnitude of vaccine responses. Methods To illustrate the impacts of co-administration of the gamma-irradiated H1N1 vaccine with poly (I:C) and recombinant murine CCL21, either alone or in combination with each other, as adjuvants on the vaccine potency, mice were inoculated intranasally 3 times at one-week interval with γ-Flu alone or with any of the three adjuvant combinations and then challenged with a high lethal dose (10 LD50) of A/PR/8/34 (H1N1) influenza virus. Virus-specific humoral, mucosal, and cell-mediated immunity, as well as cytokine profiles in the spleen (IFN-γ, IL-12, and IL-4), and in the lung homogenates (IL-6 and IL-10) were measured by ELISA. The proliferative response of restimulated splenocytes was also determined by MTT assay. Results The findings showed that the co-delivery of the γ-Flu vaccine and CCL21 or Poly (I:C) significantly increased the vaccine immunogenicity compared to the non-adjuvanted vaccine, associated with more potent protection following challenge infection. However, the mice given a combination of CCL21 with poly (I:C) had strong antibody- and cell-mediated immunity, which were considerably higher than responses of mice receiving the γ-Flu vaccine with each adjuvant separately. This combination also reduced inflammatory mediator levels (notably IL-10) in lung homogenate samples. Conclusions The results indicate that adjuvantation with the CCL21 and poly (I:C) can successfully induce vigorous vaccine-mediated protection, suggesting a robust propensity for CCL21 plus poly (I:C) as a potent mucosal adjuvant.

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A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice

Vaccines ◽

10.3390/vaccines8030389 ◽

2020 ◽

Vol 8 (3) ◽

pp. 389

Author(s):

Susan Thrane ◽

Kara-Lee Aves ◽

Ida E. M Uddbäck ◽

Christoph M. Janitzek ◽

Julianna Han ◽

...

Keyword(s):

Immune Response ◽

Single Dose ◽

Pandemic Influenza ◽

Influenza A ◽

H1n1 Influenza ◽

Antigenic Drift ◽

Promising Target ◽

Flu Vaccine ◽

Neutralizing Epitopes

Due to constant antigenic drift and shift, current influenza-A vaccines need to be redesigned and administered annually. A universal flu vaccine (UFV) that provides long-lasting protection against both seasonal and emerging pandemic influenza strains is thus urgently needed. The hemagglutinin (HA) stem antigen is a promising target for such a vaccine as it contains neutralizing epitopes, known to induce cross-protective IgG responses against a wide variety of influenza subtypes. In this study, we describe the development of a UFV candidate consisting of a HAstem trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HAstem trimer, the CLP-HAstem particles induced a more potent, long-lasting immune response and were able to protect mice against both homologous and heterologous H1N1 influenza challenge, even after a single dose.

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Factors Affecting Intention among Students to Be Vaccinated against A/H1N1 Influenza: A Health Belief Model Approach

Advances in Preventive Medicine ◽

10.4061/2011/353207 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 15

Author(s):

Sharon Teitler-Regev ◽

Shosh Shahrabani ◽

Uri Benzion

Keyword(s):

Young People ◽

Health Belief Model ◽

Influenza A ◽

Health Belief ◽

H1n1 Influenza ◽

Swine Flu ◽

Factors Affecting ◽

Perceived Seriousness ◽

Flu Vaccine ◽

Belief Model

The outbreak of A/H1N1 influenza (henceforth, swine flu) in 2009 was characterized mainly by morbidity rates among young people. This study examined the factors affecting the intention to be vaccinated against the swine flu among students in Israel. Questionnaires were distributed in December 2009 among 387 students at higher-education institutions. The research questionnaire included sociodemographic characteristics and Health Belief Model principles. The results show that the factors positively affecting the intention to take the swine flu vaccine were past experience with seasonal flu shot and three HBM categories: higher levels of perceived susceptibility for catching the illness, perceived seriousness of illness, and lower levels of barriers. We conclude that offering the vaccine at workplaces may raise the intention to take the vaccine among young people in Israel.

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H1N1 influenza A outbreak among young medical staff members who received single dose of non-adjuvanted split-virion 2009 H1N1 vaccine

Human Vaccines ◽

10.4161/hv.7.1.13459 ◽

2011 ◽

Vol 7 (1) ◽

pp. 56-57 ◽

Cited By ~ 2

Author(s):

Mamiko Ohara ◽

Masaharu Tsubokura ◽

Hosokawa Naoto ◽

Masahiro Kami ◽

Takahiro Mochizuki

Keyword(s):

Single Dose ◽

Medical Staff ◽

Influenza A ◽

H1n1 Influenza ◽

H1n1 Vaccine ◽

Staff Members ◽

2009 H1n1

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An Immunization Information System to Meet Evolving Needs During the 2009-2010 Influenza A (H1N1) Vaccination Campaign

Disaster Medicine and Public Health Preparedness ◽

10.1001/dmp.2012.64 ◽

2012 ◽

Vol 6 (4) ◽

pp. 402-407 ◽

Cited By ~ 1

Author(s):

Stephanie L. Schauer ◽

Daniel J. Hopfensperger ◽

Matthew J. Verdon ◽

Thomas R. Maerz ◽

Gerald W. Gabor ◽

...

Keyword(s):

Influenza A ◽

Local Level ◽

Vaccination Campaign ◽

Data Entry ◽

H1n1 Influenza ◽

H1n1 Vaccine ◽

Immunization Registry ◽

Influenza A H1n1 ◽

Immunization Information System ◽

Immunization Campaign

ABSTRACTIn 2009, a monovalent H1N1 influenza (H1N1) vaccine was manufactured in response to the pandemic of 2009 influenza A (H1N1) virus infection that emerged earlier in the year. The overall allocation of the H1N1 vaccine to the states was the purview of the federal government; thereafter, the states were accountable for distributing and reporting the number of doses of H1N1 vaccine administered weekly. This report describes how the Wisconsin Immunization Registry (WIR) was updated and used during the H1N1 immunization campaign and its role in meeting the federal H1N1 immunization reporting requirements. Activities to enhance the registry's functionality included the creation of a rapid data entry screen for providers to facilitate the entry of data into the WIR, and enhancing the reporting capabilities of the WIR to generate H1N1-related reports at the local level. Results of these activities included an increase in the number of WIR users, higher reported numbers of seasonal influenza doses administered, and the establishment of data streams from new users. Data completeness, the ability to accurately forecast doses needed, and validating administered doses were challenges in the changing environment.(Disaster Med Public Health Preparedness. 2012;6:402-407)

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Long-Term Immunogenicity of an Inactivated Split-Virion 2009 Pandemic Influenza A H1N1 Virus Vaccine with or without Aluminum Adjuvant in Mice

Clinical and Vaccine Immunology ◽

10.1128/cvi.00662-14 ◽

2015 ◽

Vol 22 (3) ◽

pp. 327-335 ◽

Cited By ~ 5

Author(s):

Wenting Xu ◽

Mei Zheng ◽

Feng Zhou ◽

Ze Chen

Keyword(s):

Pandemic Influenza ◽

Influenza A ◽

H1n1 Virus ◽

Effective Means ◽

Lethal Dose ◽

Igg Antibody ◽

H1n1 Vaccine ◽

Influenza A H1n1 ◽

Homologous Virus

ABSTRACTIn 2009, a global epidemic of influenza A(H1N1) virus caused the death of tens of thousands of people. Vaccination is the most effective means of controlling an epidemic of influenza and reducing the mortality rate. In this study, the long-term immunogenicity of influenza A/California/7/2009 (H1N1) split vaccine was observed as long as 15 months (450 days) after immunization in a mouse model. Female BALB/c mice were immunized intraperitoneally with different doses of aluminum-adjuvanted vaccine. The mice were challenged with a lethal dose (10× 50% lethal dose [LD50]) of homologous virus 450 days after immunization. The results showed that the supplemented aluminum adjuvant not only effectively enhanced the protective effect of the vaccine but also reduced the immunizing dose of the vaccine. In addition, the aluminum adjuvant enhanced the IgG antibody level of mice immunized with the H1N1 split vaccine. The IgG level was correlated to the survival rate of the mice. Aluminum-adjuvanted inactivated split-virion 2009 pandemic influenza A H1N1 vaccine has good immunogenicity and provided long-term protection against lethal influenza virus challenge in mice.

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Protective cellular and mucosal immune responses following nasal administration of a whole gamma-irradiated influenza A (subtype H1N1) vaccine adjuvanted with interleukin-28B in a mouse model

Archives of Virology ◽

10.1007/s00705-020-04900-3 ◽

2021 ◽

Author(s):

Ailar Sabbaghi ◽

Mohsen Zargar ◽

Mohammad Reza Zolfaghari ◽

Farahnaz Motamedi-Sedeh ◽

Amir Ghaemi

Keyword(s):

Mouse Model ◽

Immune Responses ◽

Influenza A ◽

Nasal Administration ◽

H1n1 Vaccine ◽

Interleukin 28B ◽

Mucosal Immune Responses ◽

Gamma Irradiated

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Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice

10.1101/346866 ◽

2018 ◽

Cited By ~ 1

Author(s):

Joshua D. Chandler ◽

Xin Hu ◽

Eunju Ko ◽

Soojin Park ◽

Jolyn Fernandes ◽

...

Keyword(s):

Influenza Virus ◽

Influenza A ◽

Low Dose ◽

Immune Cell ◽

Inflammatory Responses ◽

Lethal Dose ◽

Inflammatory Cells ◽

H1n1 Influenza ◽

H1n1 Infection ◽

Cell Counts

AbstractBACKGROUNDCadmium (Cd) is a toxic, pro-inflammatory metal ubiquitous in the diet that accumulates in body organs due to inefficient elimination. Many individuals exposed to dietary Cd are also infected by seasonal influenza virus. The H1N1 strain causes mild to severe pneumonia which can be fatal.OBJECTIVESTo determine the influence of low-dose Cd exposure on inflammatory responses to H1N1 influenza A virus.METHODSWe exposed mice to low-dose (1 mg CdCl2/l) Cd or vehicle (water) for 16 weeks prior to infection with a sub-lethal dose of H1N1. Lung inflammation was assessed by histopathology and flow cytometry. We used a combination of transcriptomics, metabolomics and bioinformatics to determine the molecular associations of inflammatory cells important in Cd-exacerbated responses.RESULTSCd-treated mice had increased lung tissue inflammatory cells, including neutrophils, monocytes, T lymphocytes and dendritic cells, following H1N1 infection. Lung genetic responses to infection (increasing TNF-a, interferon and complement, and decreasing myogenesis) were also exacerbated. Global correlations with immune cell counts, leading edge gene transcripts and metabolites revealed that Cd increased correlation of myeloid immune cells with pro-inflammatory genes, particularly interferon-γ, and metabolites in amino acid, nucleobase, glycerophospholipid and vitamin B3 pathways.DISCUSSIONCd burden in mice increased inflammation in response to sub-lethal H1N1 challenge, which was coordinated by genetic and metabolic responses, and could provide new targets for intervention against lethal inflammatory pathology of clinical H1N1 infection.

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