Immune Responses against a New HIV-1 p24-gp41/pCAGGS-IL-12 DNA Vaccine in Balb/c Mice.
Identifieur interne : 001937 ( Main/Exploration ); précédent : 001936; suivant : 001938Immune Responses against a New HIV-1 p24-gp41/pCAGGS-IL-12 DNA Vaccine in Balb/c Mice.
Auteurs : Fatemeh Roodbari [Iran] ; Farzaneh Sabahi [Iran] ; Mohamad Nabi Sarbolouki [Iran] ; Farzaneh Barkhordari [Iran] ; Ahmad Adeli [Iran] ; Amel Jamedar [Iran] ; Fereidoun Mahboudi [Iran]Source :
- Iranian Journal of Immunology [ 1735-1383 ] ; 2012-06.
Abstract
Background: Development of an effective vaccine is highly needed in order to restrict the AIDS pandemic. DNA vaccines initiate both arms of immunity without the potential of causing disease. HIV-1 p24 and gp41 (gag and env) proteins play important roles in viral pathogenesis and are effective candidates for immune induction and vaccine design. Objective: In this study, new DNA vaccine candidates constructed from HIV-1 fused p24-gp41 or gp41 alone were evaluated in Balb/c mice for induction of cellular and humoral immune responses. Methods: Recombinant plasmids, pcDNA3.1/Hygro expression vector containing immunogenic sequences of fused p24-gp41 or gp41alone were produced. Dendrosome used as a system for carrying vectors in laboratory animals, and an IL-12 containing vector (pCAGGS-IL-12) was co-immunized with the p24-gp41 vector as a genetic adjuvant. Induction of effective immune responses against the designed vectors as DNA vaccine candidates in Balb/c mice was evaluated. Levels of total antibodies, IgG isotypes (IgG2a and IgG1); IFN-γ and IL-4 were measured by ELISA. MTT assay was used to evaluate lymphoproliferation. Results: The results confirmed that the immunogenic epitopes of both p24 and gp41 genes are highly effective inducers of immune responses, and administration of fused p24-gp41 alone or along with IL-12 resulted in further enhancement of immune responses. Group 4 that received fused fragments (p24-gp41) along with an IL-12 expressing vector demonstrated a significantly higher Stimulation Index (SI) and IFN-γ production (p<0.0001) with a significant increase in IgG2a/IgG1 ratio, indicating the stimulation of CMI towards Th1. Although gp41 containing vector (group 6) also showed significant increases in both proliferation and IFN-γ production, the responses were persistently lower than that of p24-gp41 containing vectors. Total antibody production was highest in group 6 as expected. Conclusion: Dendrosome proved to be an efficient carrier of recombinant plasmids constructed in this study. Further studies are necessary to evaluate these constructs as HIV vaccine candidates.
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type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-197295" type="direct"><org type="institution" xml:id="struct-197295" status="VALID"> <orgName>Tarbiat Modares University [Tehran]</orgName> <desc> <address> <addrLine>Jalal Ale Ahmad Highway, P.O.Box: 14115-111, Tehran</addrLine> <country key="IR"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>Iran</country></affiliation></author><author><name sortKey="Sabahi, Farzaneh" sort="Sabahi, Farzaneh" uniqKey="Sabahi F" first="Farzaneh" last="Sabahi">Farzaneh Sabahi</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-226486" status="INCOMING"> <orgName>Department of Virology, Faculty of Medical Sciences</orgName> <desc> <address> <addrLine>Tehran , Iran</addrLine> <country key="IR"></country> </address> <ref type="url">http://www.modares.ac.ir/en/Schools/med/grp/vir</ref> </desc> <listRelation> <relation active="#struct-197295" 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Adeli</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-206859" status="VALID"> <orgName>Biotechnology Research Center</orgName> <desc> <address> <addrLine>Tehran</addrLine> <country key="IR"></country> </address> </desc> <listRelation> <relation active="#struct-55944" type="direct"></relation> <relation active="#struct-301247" type="indirect"></relation> </listRelation> <tutelles><tutelle active="#struct-55944" type="direct"><org type="institution" xml:id="struct-55944" status="VALID"> <orgName>Institut Pasteur d'Iran</orgName> <desc> <address> <addrLine>69 avenue Pasteur Téhéran 13164</addrLine> <country key="IR"></country> </address> <ref type="url">http://www.pasteur.ac.ir/</ref> </desc> <listRelation> <relation active="#struct-301247" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-301247" type="indirect"><org type="regroupinstitution" xml:id="struct-301247" status="VALID"> <orgName>Réseau International des Instituts Pasteur</orgName> <orgName type="acronym">RIIP</orgName> <desc> <address> <addrLine>25, rue du Dr Roux 75724 Paris Cedex 15</addrLine> <country key="FR"></country> </address> <ref type="url">https://research.pasteur.fr/ip-network</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>Iran</country></affiliation></author><author><name sortKey="Jamedar, Amel" sort="Jamedar, Amel" uniqKey="Jamedar A" first="Amel" last="Jamedar">Amel Jamedar</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-226489" status="INCOMING"> <orgName>Department of Microbiology and Virology, Faculty of Medicine</orgName> <desc> <address> <addrLine>Mashad</addrLine> <country key="IR"></country> </address> <ref type="url">http://www.mums.ac.ir/medical/en/index</ref> </desc> <listRelation> <relation active="#struct-354938" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-354938" type="direct"><org type="institution" xml:id="struct-354938" status="INCOMING"> <orgName>Mashad University of Medical Sciences</orgName> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>Iran</country></affiliation></author><author><name sortKey="Mahboudi, Fereidoun" sort="Mahboudi, Fereidoun" uniqKey="Mahboudi F" first="Fereidoun" last="Mahboudi">Fereidoun Mahboudi</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-206859" status="VALID"> <orgName>Biotechnology Research Center</orgName> <desc> <address> <addrLine>Tehran</addrLine> <country key="IR"></country> </address> </desc> <listRelation> <relation active="#struct-55944" type="direct"></relation> <relation active="#struct-301247" type="indirect"></relation> </listRelation> <tutelles><tutelle active="#struct-55944" type="direct"><org type="institution" xml:id="struct-55944" status="VALID"> <orgName>Institut Pasteur d'Iran</orgName> <desc> <address> <addrLine>69 avenue Pasteur Téhéran 13164</addrLine> <country key="IR"></country> </address> <ref type="url">http://www.pasteur.ac.ir/</ref> </desc> <listRelation> <relation active="#struct-301247" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-301247" type="indirect"><org type="regroupinstitution" xml:id="struct-301247" status="VALID"> <orgName>Réseau International des Instituts Pasteur</orgName> <orgName type="acronym">RIIP</orgName> <desc> <address> <addrLine>25, rue du Dr Roux 75724 Paris Cedex 15</addrLine> <country key="FR"></country> </address> <ref type="url">https://research.pasteur.fr/ip-network</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>Iran</country></affiliation></author></analytic><series><title level="j">Iranian Journal of Immunology</title><idno type="ISSN">1735-1383</idno><imprint><date type="datePub">2012-06</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="it"><term>DNA Vaccine</term><term>Dendrosome</term><term>HIV-1</term><term>IL-12</term><term>gp41</term><term>p24</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"> <p>Background: Development of an effective vaccine is highly needed in order to restrict the AIDS pandemic. DNA vaccines initiate both arms of immunity without the potential of causing disease. HIV-1 p24 and gp41 (gag and env) proteins play important roles in viral pathogenesis and are effective candidates for immune induction and vaccine design. Objective: In this study, new DNA vaccine candidates constructed from HIV-1 fused p24-gp41 or gp41 alone were evaluated in Balb/c mice for induction of cellular and humoral immune responses. Methods: Recombinant plasmids, pcDNA3.1/Hygro expression vector containing immunogenic sequences of fused p24-gp41 or gp41alone were produced. Dendrosome used as a system for carrying vectors in laboratory animals, and an IL-12 containing vector (pCAGGS-IL-12) was co-immunized with the p24-gp41 vector as a genetic adjuvant. Induction of effective immune responses against the designed vectors as DNA vaccine candidates in Balb/c mice was evaluated. Levels of total antibodies, IgG isotypes (IgG2a and IgG1); IFN-γ and IL-4 were measured by ELISA. MTT assay was used to evaluate lymphoproliferation. Results: The results confirmed that the immunogenic epitopes of both p24 and gp41 genes are highly effective inducers of immune responses, and administration of fused p24-gp41 alone or along with IL-12 resulted in further enhancement of immune responses. Group 4 that received fused fragments (p24-gp41) along with an IL-12 expressing vector demonstrated a significantly higher Stimulation Index (SI) and IFN-γ production (p<0.0001) with a significant increase in IgG2a/IgG1 ratio, indicating the stimulation of CMI towards Th1. Although gp41 containing vector (group 6) also showed significant increases in both proliferation and IFN-γ production, the responses were persistently lower than that of p24-gp41 containing vectors. Total antibody production was highest in group 6 as expected. Conclusion: Dendrosome proved to be an efficient carrier of recombinant plasmids constructed in this study. Further studies are necessary to evaluate these constructs as HIV vaccine candidates.</p> </div></front></TEI><affiliations><list><country><li>Iran</li></country></list><tree><country name="Iran"><noRegion><name sortKey="Roodbari, Fatemeh" sort="Roodbari, Fatemeh" uniqKey="Roodbari F" first="Fatemeh" last="Roodbari">Fatemeh Roodbari</name></noRegion><name sortKey="Adeli, Ahmad" sort="Adeli, Ahmad" uniqKey="Adeli A" first="Ahmad" last="Adeli">Ahmad Adeli</name><name sortKey="Barkhordari, Farzaneh" sort="Barkhordari, Farzaneh" uniqKey="Barkhordari F" first="Farzaneh" last="Barkhordari">Farzaneh Barkhordari</name><name sortKey="Jamedar, Amel" sort="Jamedar, Amel" uniqKey="Jamedar A" first="Amel" last="Jamedar">Amel Jamedar</name><name sortKey="Mahboudi, Fereidoun" sort="Mahboudi, Fereidoun" uniqKey="Mahboudi F" first="Fereidoun" last="Mahboudi">Fereidoun Mahboudi</name><name sortKey="Sabahi, Farzaneh" sort="Sabahi, Farzaneh" uniqKey="Sabahi F" first="Farzaneh" last="Sabahi">Farzaneh Sabahi</name><name sortKey="Sarbolouki, Mohamad Nabi" sort="Sarbolouki, Mohamad Nabi" uniqKey="Sarbolouki M" first="Mohamad Nabi" last="Sarbolouki">Mohamad Nabi Sarbolouki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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