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Azharuddin, M., Zhu, G. H., Sengupta, A., Hinkula, J., Slater, N. K. .. & Patra, H. (2022). Nano toolbox in immune modulation and nanovaccines. Trends in Biotechnology, 40(10), 1195-1212
Open this publication in new window or tab >>Nano toolbox in immune modulation and nanovaccines
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2022 (English)In: Trends in Biotechnology, ISSN 0167-7799, E-ISSN 1879-3096, Vol. 40, no 10, p. 1195-1212Article, review/survey (Refereed) Published
Abstract [en]

Despite the great success of vaccines over two centuries, the conventional strategy is based on attenuated/altered microorganisms. However, this is not effective for all microbes and often fails to elicit a protective immune response, and sometimes poses unexpected safety risks. The expanding nano toolbox may overcome some of the roadblocks in vaccine development given the plethora of unique nanoparticle (NP)-based platforms that can successfully induce specific immune responses leading to exciting and novel solutions. Nanovaccines necessitate a thorough understanding of the immunostimulatory effect of these nanotools. We present a comprehensive description of strategies in which nanotools have been used to elicit an immune response and provide a perspective on how nanotechnology can lead to future personalized nanovaccines.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Elsevier, 2022
Keywords
vaccine, nano toolbox, nanovaccine, immune modulation, immune response
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-186124 (URN)10.1016/j.tibtech.2022.03.011 (DOI)000865425700007 ()35450779 (PubMedID)2-s2.0-85128672095 (Scopus ID)
Note

Funding: EU [706694]; UK Medical Research Council Career Development Award [MR/T030968/1]; British Council; UK -India Education and Research Initiative (UKIERI); Government of India [P325]; Sister Nibedita Government General Degree College for Girls (India)

Available from: 2022-06-20 Created: 2022-06-20 Last updated: 2023-09-15Bibliographically approved
Omer, A. A. M., Hinkula, J., Pham-Tue-Hung, T., Melik, W., Zattarin, E., Aili, D., . . . Khalaf, H. (2022). Plantaricin NC8 alpha beta rapidly and efficiently inhibits flaviviruses and SARS-CoV-2 by disrupting their envelopes. PLOS ONE, 17(11), Article ID e0278419.
Open this publication in new window or tab >>Plantaricin NC8 alpha beta rapidly and efficiently inhibits flaviviruses and SARS-CoV-2 by disrupting their envelopes
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2022 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 11, article id e0278419Article in journal (Refereed) Published
Abstract [en]

Potent broad-spectrum antiviral agents are urgently needed to combat existing and emerging viral infections. This is particularly important considering that vaccine development is a costly and time consuming process and that viruses constantly mutate and render the vaccine ineffective. Antimicrobial peptides (AMP), such as bacteriocins, are attractive candidates as antiviral agents against enveloped viruses. One of these bacteriocins is PLNC8 alpha beta, which consists of amphipathic peptides with positive net charges that display high affinity for negatively charged pathogen membrane structures, including phosphatidylserine rich lipid membranes of viral envelopes. Due to the morphological and physiological differences between viral envelopes and host cell plasma membranes, PLNC8 alpha beta is thought to have high safety profile by specifically targeting viral envelopes without effecting host cell membranes. In this study, we have tested the antiviral effects of PLNC8 alpha beta against the flaviviruses Langat and Kunjin, coronavirus SARS-CoV-2, influenza A virus (IAV), and human immunodeficiency virus-1 (HIV-1). The concentration of PLNC8 alpha beta that is required to eliminate all the infective virus particles is in the range of nanomolar (nM) to micromolar (mu M), which is surprisingly efficient considering the high content of cholesterol (8-35%) in their lipid envelopes. We found that viruses replicating in the endoplasmic reticulum (ER)/Golgi complex, e.g. SARS-CoV-2 and flaviviruses, are considerably more susceptible to PLNC8 alpha beta, compared to viruses that acquire their lipid envelope from the plasma membrane, such as IAV and HIV-1. Development of novel broad-spectrum antiviral agents can significantly benefit human health by rapidly and efficiently eliminating infectious virions and thereby limit virus dissemination and spreading between individuals. PLNC8 alpha beta can potentially be developed into an effective and safe antiviral agent that targets the lipid compartments of viral envelopes of extracellular virions, more or less independent of virus antigenic mutations, which faces many antiviral drugs and vaccines.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2022
National Category
Infectious Medicine
Identifiers
urn:nbn:se:liu:diva-191617 (URN)10.1371/journal.pone.0278419 (DOI)000905496400010 ()36449554 (PubMedID)
Note

Funding Agencies|Knowledge Foundation, Sweden, TB [20180148]

Available from: 2023-02-05 Created: 2023-02-05 Last updated: 2023-02-05
Cardona Gomez, M. E., Hinkula, J., Gustafsson, K., Christensson, B., Wahren, B., Mohamed, A. J., . . . Arteaga, H. J. (2022). Specific properties of shRNA-mediated CCR5 downregulation that enhance the inhibition of HIV-1 infection in combination with shRNA targeting HIV-1 rev. Molecular Biology Reports, 49, 11187-11192
Open this publication in new window or tab >>Specific properties of shRNA-mediated CCR5 downregulation that enhance the inhibition of HIV-1 infection in combination with shRNA targeting HIV-1 rev
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2022 (English)In: Molecular Biology Reports, ISSN 0301-4851, E-ISSN 1573-4978, Vol. 49, p. 11187-11192Article in journal (Refereed) Published
Abstract [en]

Treatment with RNAi against HIV-1 transcripts efficiently inhibits viral replication but induces selection of escape mutants; therefore, the CCR5 coreceptor was suggested as an additional target. Blocking viral and host transcripts improved the antiviral effect. We have used short hairpin RNA (shRNA) targeting the human CCR5 (shCCR5) or the HIV-1 rev (shRev) transcripts to demonstrate distinctive properties of anti-CCR5 shRNA: shCCR5 induced more sustained protection than shRev; partial reduction in CCR5 expression substantially decreased HIV-1 infection, and shCCR5 performed better than shRev in the mixed shRNA-treated and untreated cultures. These observations indicate that CCR5 inhibitors should be conveniently included in HIV-1 gene silencing treatment schedules when only a certain cell fraction is protected to further reduce endogenous virus in a properly ART-treated HIV-1 infected individual.

Place, publisher, year, edition, pages
Springer, 2022
Keywords
RNA interference; HIV-1; Rev gene; CCR5 receptor
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-188583 (URN)10.1007/s11033-022-07899-9 (DOI)000853292200001 ()36098885 (PubMedID)
Note

Funding Agencies|Corporacion para el Desarrollo de la Ciencia y la Tecnologia

Available from: 2022-09-19 Created: 2022-09-19 Last updated: 2023-03-07Bibliographically approved
Patra, H. K., Azharuddin, M., Islam, M. M., Papapavlou, G., Deb, S., Osterrieth, J., . . . Slater, N. K. H. (2019). Rational Nanotoolbox with Theranostic Potential for Medicated Pro-Regenerative Corneal Implants. Advanced Functional Materials, 29(38), Article ID 1903760.
Open this publication in new window or tab >>Rational Nanotoolbox with Theranostic Potential for Medicated Pro-Regenerative Corneal Implants
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2019 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 29, no 38, article id 1903760Article in journal (Refereed) Published
Abstract [en]

Cornea diseases are a leading cause of blindness and the disease burden is exacerbated by the increasing shortage around the world for cadaveric donor corneas. Despite the advances in the field of regenerative medicine, successful transplantation of laboratory‐made artificial corneas is not fully realized in clinical practice. The causes of failure of such artificial corneal implants are multifactorial and include latent infections from viruses and other microbes, enzyme overexpression, implant degradation, extrusion or delayed epithelial regeneration. Therefore, there is an urgent unmet need for developing customized corneal implants to suit the host environment and counter the effects of inflammation or infection, which are able to track early signs of implant failure in situ. This work reports a nanotoolbox comprising tools for protection from infection, promotion of regeneration, and noninvasive monitoring of the in situ corneal environment. These nanosystems can be incorporated within pro‐regenerative biosynthetic implants, transforming them into theranostic devices, which are able to respond to biological changes following implantation.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
herpes simplex virus type 1 (HSV-1), magnetic resonance imaging (MRI), premedicated cornea implants, pro-regeneration, theranostics
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-159097 (URN)10.1002/adfm.201903760 (DOI)000476281800001 ()2-s2.0-85069940064 (Scopus ID)
Note

Funding agencies: EU H2020 Marie Sklodowska-Curie Individual Fellowship [706694]; MIIC Strategic Postdoc Grant; MIIC Seed Grant at Linkoping University (LiU), Sweden

Available from: 2019-07-24 Created: 2019-07-24 Last updated: 2023-02-22Bibliographically approved
Falkeborn, T., Asahara, N., Hayashi, M., Arai, M., Hinkula, J. & Maltais, A.-K. (2015). Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum. Jacobs Journal of Vaccine and Vaccination, 1(1), Article ID 006.
Open this publication in new window or tab >>Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum
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2015 (English)In: Jacobs Journal of Vaccine and Vaccination, ISSN 2381-2664, Vol. 1, no 1, article id 006Article in journal (Refereed) Published
Abstract [en]

To enable efficient mucosal vaccination with split or subunit antigens, an adjuvant is often needed. To date, no mucosal adjuvants are approved for human use, however, there are a variety of mucosal adjuvants in development, including the liposome-based adjuvant Endocine™. The aim of this study was to evaluate split influenza antigens together with Endocine™ and in order to assess the potency of Endocine™, the induction of humoral immune responses were compared to those following influenza vaccination with cholera toxin (CT) or aluminum salt (alum). We show that Endocine™ significantly enhances influenza-specific immune responses in intranasally immunized mice compared to nonadjuvanted vaccine. Furthermore, vaccines adjuvanted with Endocine™ evoked comparable serum IgG and virus neutralizing (VN) antibody titers as nasal vaccines adjuvanted with CT. Compared to parenteral vaccination with alum, Endocine™ triggered significantly higher mucosal and serum IgA titers, and similar VN titers. Taken together, these results support further development of Endocine™ as a mucosal adjuvant and as part of a nasal influenza vaccine candidate.

Place, publisher, year, edition, pages
Jacobs Publishers, 2015
Keywords
Mucosal adjuvant; nasal immunization; vaccine; Endocine; influenza; neutralizing antibodies
National Category
Clinical Laboratory Medicine Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-117979 (URN)
Available from: 2015-05-19 Created: 2015-05-19 Last updated: 2018-01-11Bibliographically approved
Ellegård, R., Crisci, E., Andersson, J., Shankar, E. M., Nyström, S., Hinkula, J. & Larsson, M. (2015). Impaired NK Cell Activation and Chemotaxis toward Dendritic Cells Exposed to Complement-Opsonized HIV-1. Journal of Immunology, 195(4), 1698-1704
Open this publication in new window or tab >>Impaired NK Cell Activation and Chemotaxis toward Dendritic Cells Exposed to Complement-Opsonized HIV-1
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2015 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 195, no 4, p. 1698-1704Article in journal (Refereed) Published
Abstract [en]

Mucosa resident dendritic cells (DCs) may represent one of the first immune cells that HIV-1 encounters during sexual transmission. The virions in body fluids can be opsonized with complement factors because of HIV-mediated triggering of the complement cascade, and this appears to influence numerous aspects of the immune defense targeting the virus. One key attribute of host defense is the ability to attract immune cells to the site of infection. In this study, we investigated whether the opsonization of HIV with complement (C-HIV) or a mixture of complement and Abs (CI-HIV) affected the cytokine and chemokine responses generated by DCs, as well as their ability to attract other immune cells. We found that the expression levels of CXCL8, CXCL10, CCL3, and CCL17 were lowered after exposure to either C-HIV or CI-HIV relative to free HIV (F-HIV). DCs exposed to F-HIV induced higher cell migration, consisting mainly of NK cells, compared with opsonized virus, and the chemotaxis of NK cells was dependent on CCL3 and CXCL10. NK cell exposure to supernatants derived from HIV-exposed DCs showed that F-HIV induced phenotypic activation (e.g., increased levels of TIM3, CD69, and CD25) and effector function (e.g., production of IFN gamma and killing of target cells) in NK cells, whereas C-HIV and CI-HIV did not. The impairment of NK cell recruitment by DCs exposed to complement-opsonized HIV and the lack of NK activation may contribute to the failure of innate immune responses to control HIV at the site of initial mucosa infection.

Place, publisher, year, edition, pages
American Association of Immunologists, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-121313 (URN)10.4049/jimmunol.1500618 (DOI)000360013200039 ()26157174 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Swedish Physicians against AIDS Research Foundation [AI52731]; Swedish International Development Cooperation Agency/Swedish Agency for Research Cooperation with Developing Countries-Special Assistant; VINNMER for Vinnova; Linkoping University Hospital Research Fund; central regional agreement on medical training and clinical research (CALF) between Ostergotland County Council and Linkoping University; Swedish Society of Medicine; High Impact Research; University of Malaya [UM.C.625/1/HIR/139]

Available from: 2015-09-16 Created: 2015-09-14 Last updated: 2021-12-29
Ellegård, R., Crisci, E., Burgener, A., Sjöwall, C., Birse, K., Westmacott, G., . . . Larsson, M. (2014). Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3. Journal of Immunology, 193(9), 4590-4601
Open this publication in new window or tab >>Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3
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2014 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 193, no 9, p. 4590-4601Article in journal (Refereed) Published
Abstract [en]

Immature dendritic cells (iDCs) in genital and rectal mucosa may be one of the first cells to come into contact with HIV-1 during sexual transmission of virus. HIV-1 activates the host complement system, which results in opsonization of virus by inactivated complement fragments, for example, iC3b. We investigated antiviral and inflammatory responses induced in human iDCs after exposure to free HIV-1 (F-HIV), complement-opsonized HIV-1 (C-HIV), and complement and Ab-opsonized HIV-1 (CI-HIV). F-HIV gave rise to a significantly higher expression of antiviral factors such as IFN-beta, myxovirus resistance protein A, and IFN-stimulated genes, compared with C-HIV and CI-HIV. Additionally, F-HIV induced inflammatory factors such as IL-1 beta, IL-6, and TNF-alpha, whereas these responses were weakened or absent after C-HIV or CI-HIV exposure. The responses induced by F-HIV were TLR8-dependent with subsequent activation of IFN regulatory factor 1, p38, ERK, PI3K, and NF-kappa B pathways, whereas these responses were not induced by C-HIV, which instead induced activation of IFN regulatory factor 3 and Lyn. This modulation of TLR8 signaling was mediated by complement receptor 3 and led to enhanced infection. The impact that viral hijacking of the complement system has on iDC function could be an important immune evasion mechanism used by HIV-1 to establish infection in the host.

Place, publisher, year, edition, pages
American Association of Immunologists, 2014
National Category
Basic Medicine
Identifiers
urn:nbn:se:liu:diva-112625 (URN)10.4049/jimmunol.1401781 (DOI)000344079500033 ()25252956 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; VINNMER for Vinnova; Linkoping University Hospital Research Fund Grant C-ALF; Swedish Society of Medicine; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Swedish Society for Medical Research

Available from: 2014-12-08 Created: 2014-12-05 Last updated: 2018-09-28Bibliographically approved
Oynebraten, I., Hinkula, J., Fredriksen, A. B. & Bogen, B. (2014). Increased Generation of HIV-1 gp120-Reactive CD8(+) T Cells by a DNA Vaccine Construct Encoding the Chemokine CCL3. PLOS ONE, 9(8), e104814
Open this publication in new window or tab >>Increased Generation of HIV-1 gp120-Reactive CD8(+) T Cells by a DNA Vaccine Construct Encoding the Chemokine CCL3
2014 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 8, p. e104814-Article in journal (Refereed) Published
Abstract [en]

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.

Place, publisher, year, edition, pages
Public Library of Science, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-110974 (URN)10.1371/journal.pone.0104814 (DOI)000341017000062 ()25122197 (PubMedID)
Note

Funding Agencies|Research Council of Norway; Odd Fellow

Available from: 2014-10-01 Created: 2014-10-01 Last updated: 2021-06-14
Timpka, T., Spreco, A., Gursky, E., Eriksson, O., Dahlström, Ö., Strömgren, M., . . . Holm, E. (2014). Intentions to perform non-pharmaceutical protective behaviors during influenza outbreaks in Sweden: a cross-sectional study following a mass vaccination campaign. PLOS ONE, 9(3), e91060
Open this publication in new window or tab >>Intentions to perform non-pharmaceutical protective behaviors during influenza outbreaks in Sweden: a cross-sectional study following a mass vaccination campaign
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2014 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 3, p. e91060-Article in journal (Refereed) Published
Abstract [en]

Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45–85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non-pharmaceutical health actions in the Swedish outlined context, and that variations in threat appraisal played a smaller role in these models despite scientific uncertainties surrounding a recent mass vaccination campaign.

Place, publisher, year, edition, pages
Public Library of Science, 2014
National Category
Health Sciences
Identifiers
urn:nbn:se:liu:diva-105029 (URN)10.1371/journal.pone.0091060 (DOI)000332485800091 ()
Available from: 2014-03-06 Created: 2014-03-06 Last updated: 2021-06-14Bibliographically approved
Maltais, A.-K., Stittelaar, K. J., Veldhuis Kroeze, E. J., van Amerongen, G., Dijkshoorn, M. L., Krestin, G. P., . . . Osterhaus, A. D. (2014). Intranasally administered Endocine™ formulated 2009 pandemic influenza H1N1 vaccine induces broad specific antibody responses and confers protection in ferrets. Vaccine, 32(26), 3307-15
Open this publication in new window or tab >>Intranasally administered Endocine™ formulated 2009 pandemic influenza H1N1 vaccine induces broad specific antibody responses and confers protection in ferrets
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2014 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 32, no 26, p. 3307-15Article in journal (Refereed) Published
Abstract [en]

Influenza is a contagious respiratory disease caused by an influenza virus. Due to continuous antigenic drift of seasonal influenza viruses, influenza vaccines need to be adjusted before every influenza season. This allows annual vaccination with multivalent seasonal influenza vaccines, recommended especially for high-risk groups. There is a need for a seasonal influenza vaccine that induces broader and longer lasting protection upon easy administration. Endocine™ is a lipid-based mucosal adjuvant composed of endogenous lipids found ubiquitously in the human body. Intranasal administration of influenza antigens mixed with this adjuvant has been shown to induce local and systemic immunity as well as protective efficacy against homologous influenza virus challenge in mice. Here we used ferrets, an established animal model for human influenza virus infections, to further investigate the potential of Endocine™ as an adjuvant. Intranasal administration of inactivated pandemic H1N1/California/2009 split antigen or whole virus antigen mixed with Endocine™ induced high levels of serum hemagglutination inhibition (HI) and virus neutralization (VN) antibody titers that were also cross reactive against distant swine viruses of the same subtype. HI and VN antibody titers were already demonstrated after a single nasal immunization. Upon intratracheal challenge with a homologous challenge virus (influenza virus H1N1/The Netherlands/602/2009) immunized ferrets were fully protected from virus replication in the lungs and largely protected against body weight loss, virus replication in the upper respiratory tract and pathological changes in the respiratory tract. Endocine™ formulated vaccines containing split antigen induced higher HI and VN antibody responses and better protection from body weight loss and virus shedding in the upper respiratory tract than the Endocine™ formulated vaccine containing whole virus antigen.

National Category
Basic Medicine Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-106769 (URN)10.1016/j.vaccine.2014.03.061 (DOI)000336872500028 ()24690149 (PubMedID)2-s2.0-84900393484 (Scopus ID)
Available from: 2014-05-22 Created: 2014-05-22 Last updated: 2019-02-01
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-1908-5609

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