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A pandemic influenza H1N1 live vaccine based on modified vaccinia Ankara is highly immunogenic and protects mice in active and passive immunizations.
PLoS One. 2010 Aug 16; 5(8):e12217.Plos

Abstract

BACKGROUND

The development of novel influenza vaccines inducing a broad immune response is an important objective. The aim of this study was to evaluate live vaccines which induce both strong humoral and cell-mediated immune responses against the novel human pandemic H1N1 influenza virus, and to show protection in a lethal animal challenge model.

METHODOLOGY/PRINCIPAL FINDINGS

For this purpose, the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza A/California/07/2009 (H1N1) strain (CA/07) were inserted into the replication-deficient modified vaccinia Ankara (MVA) virus--a safe poxviral live vector--resulting in MVA-H1-Ca and MVA-N1-Ca vectors. These live vaccines, together with an inactivated whole virus vaccine, were assessed in a lung infection model using immune competent Balb/c mice, and in a lethal challenge model using severe combined immunodeficient (SCID) mice after passive serum transfer from immunized mice. Balb/c mice vaccinated with the MVA-H1-Ca virus or the inactivated vaccine were fully protected from lung infection after challenge with the influenza H1N1 wild-type strain, while the neuraminidase virus MVA-N1-Ca induced only partial protection. The live vaccines were already protective after a single dose and induced substantial amounts of neutralizing antibodies and of interferon-gamma-secreting (IFN-gamma) CD4- and CD8 T-cells in lungs and spleens. In the lungs, a rapid increase of HA-specific CD4- and CD8 T cells was observed in vaccinated mice shortly after challenge with influenza swine flu virus, which probably contributes to the strong inhibition of pulmonary viral replication observed. In addition, passive transfer of antisera raised in MVA-H1-Ca vaccinated immune-competent mice protected SCID mice from lethal challenge with the CA/07 wild-type virus.

CONCLUSIONS/SIGNIFICANCE

The non-replicating MVA-based H1N1 live vaccines induce a broad protective immune response and are promising vaccine candidates for pandemic influenza.

Authors+Show Affiliations

R&D Vaccines, Biomedical Research Center, Baxter BioScience, Orth/Donau, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20808939

Citation

Hessel, Annett, et al. "A Pandemic Influenza H1N1 Live Vaccine Based On Modified Vaccinia Ankara Is Highly Immunogenic and Protects Mice in Active and Passive Immunizations." PloS One, vol. 5, no. 8, 2010, pp. e12217.
Hessel A, Schwendinger M, Fritz D, et al. A pandemic influenza H1N1 live vaccine based on modified vaccinia Ankara is highly immunogenic and protects mice in active and passive immunizations. PLoS One. 2010;5(8):e12217.
Hessel, A., Schwendinger, M., Fritz, D., Coulibaly, S., Holzer, G. W., Sabarth, N., Kistner, O., Wodal, W., Kerschbaum, A., Savidis-Dacho, H., Crowe, B. A., Kreil, T. R., Barrett, P. N., & Falkner, F. G. (2010). A pandemic influenza H1N1 live vaccine based on modified vaccinia Ankara is highly immunogenic and protects mice in active and passive immunizations. PloS One, 5(8), e12217. https://doi.org/10.1371/journal.pone.0012217
Hessel A, et al. A Pandemic Influenza H1N1 Live Vaccine Based On Modified Vaccinia Ankara Is Highly Immunogenic and Protects Mice in Active and Passive Immunizations. PLoS One. 2010 Aug 16;5(8):e12217. PubMed PMID: 20808939.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A pandemic influenza H1N1 live vaccine based on modified vaccinia Ankara is highly immunogenic and protects mice in active and passive immunizations. AU - Hessel,Annett, AU - Schwendinger,Michael, AU - Fritz,Daniela, AU - Coulibaly,Sogue, AU - Holzer,Georg W, AU - Sabarth,Nicolas, AU - Kistner,Otfried, AU - Wodal,Walter, AU - Kerschbaum,Astrid, AU - Savidis-Dacho,Helga, AU - Crowe,Brian A, AU - Kreil,Thomas R, AU - Barrett,P Noel, AU - Falkner,Falko G, Y1 - 2010/08/16/ PY - 2010/01/18/received PY - 2010/07/11/accepted PY - 2010/9/3/entrez PY - 2010/9/3/pubmed PY - 2010/11/5/medline SP - e12217 EP - e12217 JF - PloS one JO - PLoS One VL - 5 IS - 8 N2 - BACKGROUND: The development of novel influenza vaccines inducing a broad immune response is an important objective. The aim of this study was to evaluate live vaccines which induce both strong humoral and cell-mediated immune responses against the novel human pandemic H1N1 influenza virus, and to show protection in a lethal animal challenge model. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza A/California/07/2009 (H1N1) strain (CA/07) were inserted into the replication-deficient modified vaccinia Ankara (MVA) virus--a safe poxviral live vector--resulting in MVA-H1-Ca and MVA-N1-Ca vectors. These live vaccines, together with an inactivated whole virus vaccine, were assessed in a lung infection model using immune competent Balb/c mice, and in a lethal challenge model using severe combined immunodeficient (SCID) mice after passive serum transfer from immunized mice. Balb/c mice vaccinated with the MVA-H1-Ca virus or the inactivated vaccine were fully protected from lung infection after challenge with the influenza H1N1 wild-type strain, while the neuraminidase virus MVA-N1-Ca induced only partial protection. The live vaccines were already protective after a single dose and induced substantial amounts of neutralizing antibodies and of interferon-gamma-secreting (IFN-gamma) CD4- and CD8 T-cells in lungs and spleens. In the lungs, a rapid increase of HA-specific CD4- and CD8 T cells was observed in vaccinated mice shortly after challenge with influenza swine flu virus, which probably contributes to the strong inhibition of pulmonary viral replication observed. In addition, passive transfer of antisera raised in MVA-H1-Ca vaccinated immune-competent mice protected SCID mice from lethal challenge with the CA/07 wild-type virus. CONCLUSIONS/SIGNIFICANCE: The non-replicating MVA-based H1N1 live vaccines induce a broad protective immune response and are promising vaccine candidates for pandemic influenza. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/20808939/A_pandemic_influenza_H1N1_live_vaccine_based_on_modified_vaccinia_Ankara_is_highly_immunogenic_and_protects_mice_in_active_and_passive_immunizations_ L2 - https://dx.plos.org/10.1371/journal.pone.0012217 DB - PRIME DP - Unbound Medicine ER -