Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication
Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, v...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-04-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396417300907 |
| _version_ | 1818920284110979072 |
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| author | Huanbin Xu Anne-Marie Andersson Emeline Ragonnaud Ditte Boilesen Anders Tolver Benjamin Anderschou Holbech Jensen James L. Blanchard Alfredo Nicosia Antonella Folgori Stefano Colloca Riccardo Cortese Allan Randrup Thomsen Jan Pravsgaard Christensen Ronald S. Veazey Peter Johannes Holst |
| author_facet | Huanbin Xu Anne-Marie Andersson Emeline Ragonnaud Ditte Boilesen Anders Tolver Benjamin Anderschou Holbech Jensen James L. Blanchard Alfredo Nicosia Antonella Folgori Stefano Colloca Riccardo Cortese Allan Randrup Thomsen Jan Pravsgaard Christensen Ronald S. Veazey Peter Johannes Holst |
| author_sort | Huanbin Xu |
| collection | DOAJ |
| description | Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P = 0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance.
In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia. |
| first_indexed | 2024-12-20T01:19:18Z |
| format | Article |
| id | doaj.art-de682d37b8db4cfeb554f35e480eb8f5 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-20T01:19:18Z |
| publishDate | 2017-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-de682d37b8db4cfeb554f35e480eb8f52022-12-21T19:58:30ZengElsevierEBioMedicine2352-39642017-04-0118C20421510.1016/j.ebiom.2017.03.003Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral ReplicationHuanbin Xu0Anne-Marie Andersson1Emeline Ragonnaud2Ditte Boilesen3Anders Tolver4Benjamin Anderschou Holbech Jensen5James L. Blanchard6Alfredo Nicosia7Antonella Folgori8Stefano Colloca9Riccardo Cortese10Allan Randrup Thomsen11Jan Pravsgaard Christensen12Ronald S. Veazey13Peter Johannes Holst14Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USACenter for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, 1014, DenmarkCenter for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, 1014, DenmarkCenter for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, 1014, DenmarkDepartment of Mathematical Sciences, University of Copenhagen, 2100, DenmarkDepartment of Biology, University of Copenhagen, 2100, DenmarkTulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USAReiThera, viale Città d'Europa 679, 00144 Rome, ItalyReiThera, viale Città d'Europa 679, 00144 Rome, ItalyReiThera, viale Città d'Europa 679, 00144 Rome, ItalyKEIRES, Bäumleingasse 18, CH 4051 Basel, SwitzerlandDepartment of Immunology and Microbiology, University of Copenhagen, 2200, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, 2200, DenmarkTulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USACenter for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, 1014, DenmarkConventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P = 0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia.http://www.sciencedirect.com/science/article/pii/S2352396417300907Heterologous viral vectored prime-boost immunizationGenetic adjuvant |
| spellingShingle | Huanbin Xu Anne-Marie Andersson Emeline Ragonnaud Ditte Boilesen Anders Tolver Benjamin Anderschou Holbech Jensen James L. Blanchard Alfredo Nicosia Antonella Folgori Stefano Colloca Riccardo Cortese Allan Randrup Thomsen Jan Pravsgaard Christensen Ronald S. Veazey Peter Johannes Holst Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication EBioMedicine Heterologous viral vectored prime-boost immunization Genetic adjuvant |
| title | Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication |
| title_full | Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication |
| title_fullStr | Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication |
| title_full_unstemmed | Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication |
| title_short | Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication |
| title_sort | mucosal vaccination with heterologous viral vectored vaccine targeting subdominant siv accessory antigens strongly inhibits early viral replication |
| topic | Heterologous viral vectored prime-boost immunization Genetic adjuvant |
| url | http://www.sciencedirect.com/science/article/pii/S2352396417300907 |
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