Tags

Type your tag names separated by a space and hit enter

Vaccination of macaques with DNA followed by adenoviral vectors encoding SIV gag alone delays infection by repeated mucosal challenge with SIV.
J Virol 2019JV

Abstract

Vaccines aimed at inducing T cell responses to protect against human immunodeficiency virus (HIV) infection have been under development for more than 15 years. Replication defective adenovirus (rAd) vaccine vectors are at the forefront of this work and tested extensively in the simian immunodeficiency virus (SIV) challenge macaque model. Vaccination with rAd vectors coding for SIV gag or other non-envelope proteins induce T cell responses that control virus load but disappointingly are unsuccessful so far in preventing infection and attention has turned to inducing antibodies to the envelope. However, here we report that Mauritian cynomologus macaques, Macaca fascicularis (MCM), vaccinated against unmodified gag alone with a DNA prime followed by a rAd boost exhibit increased protection from infection by repeated intrarectal challenge with low dose SIVmac251. There was no evidence of infection followed by eradication. A significant correlation was observed between cytokine expression by CD4 T cells and delayed infection. Vaccination with gag fused to the ubiquitin gene or fragmented, designed to increase CD8 magnitude and breadth, did not confer resistance to challenge or enhance immunity. On infection a significant reduction in peak virus load was observed in all vaccinated animals including those vaccinated with modified gag These findings suggest that a non-persistent viral vector vaccine coding for internal virus proteins may be able to protect against HIV-1 infection. The mechanisms are probably distinct from antibody-mediated virus neutralization or cytotoxic CD8 cell killing of virus infected cells and may be mediated in part by CD4 T cells.IMPORTANCE The Simian Immunodeficiency Virus (SIV) macaque model represents the best animal model for testing new HIV-1 vaccines. Previous studies employing replication defective adenovirus (rAd) vectors that transiently express SIV internal proteins induced T cell responses that controlled virus load but did not protect against virus challenge. However, we show for the first time that SIV gag delivered in a DNA prime followed by a boost with rAd vector confers resistance to SIV intrarectal challenge. Other partially successful SIV/HIV-1 protective vaccines induce antibody to envelope and neutralise the virus or mediate antibody dependent cytotoxicity. Induction of CD8 T cells which do not prevent initial infection but eradicate infected cells before infection becomes established have also shown some success. By contrast the vaccine described here mediates resistance by a different mechanism from that described above which may reflect CD4 T cell activity. This could indicate an alternative approach for HIV-1 vaccine development.

Authors+Show Affiliations

Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Controls, Hertfordshire, UK neil.almond@nibsc.org s.patterson@imperial.ac.uk.Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Controls, Hertfordshire, UK.Biotherapeutics Group, National Institute for Biological Standards and Controls, Hertfordshire, UK.Analytical Sciences Group, National Institute for Biological Standards and Controls, Hertfordshire, UK.Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Controls, Hertfordshire, UK.Division of Virology, National Institute for Biological Standards and Controls, Hertfordshire, UK.Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Controls, Hertfordshire, UK.Division of Virology, National Institute for Biological Standards and Controls, Hertfordshire, UK.Biotherapeutics Group, National Institute for Biological Standards and Controls, Hertfordshire, UK.Division of Virology, National Institute for Biological Standards and Controls, Hertfordshire, UK.Division of Virology, National Institute for Biological Standards and Controls, Hertfordshire, UK.German Primate Centre, 37077 Gottingen, Germany.School of Biological Sciences, Royal Holloway, University of London, Surrey, UK.Centre for Immunology and Vaccinology, Imperial College London, London, UK.Centre for Immunology and Vaccinology, Imperial College London, London, UK.Centre for Immunology and Vaccinology, Imperial College London, London, UK.School of Biological Sciences, Royal Holloway, University of London, Surrey, UK.Centre for Immunology and Vaccinology, Imperial College London, London, UK.Centre for Immunology and Vaccinology, Imperial College London, London, UK neil.almond@nibsc.org s.patterson@imperial.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31413132

Citation

Almond, Neil, et al. "Vaccination of Macaques With DNA Followed By Adenoviral Vectors Encoding SIV Gag Alone Delays Infection By Repeated Mucosal Challenge With SIV." Journal of Virology, 2019.
Almond N, Berry N, Stebbings R, et al. Vaccination of macaques with DNA followed by adenoviral vectors encoding SIV gag alone delays infection by repeated mucosal challenge with SIV. J Virol. 2019.
Almond, N., Berry, N., Stebbings, R., Preston, M., Ham, C., Page, M., ... Patterson, S. (2019). Vaccination of macaques with DNA followed by adenoviral vectors encoding SIV gag alone delays infection by repeated mucosal challenge with SIV. Journal of Virology, doi:10.1128/JVI.00606-19.
Almond N, et al. Vaccination of Macaques With DNA Followed By Adenoviral Vectors Encoding SIV Gag Alone Delays Infection By Repeated Mucosal Challenge With SIV. J Virol. 2019 Aug 14; PubMed PMID: 31413132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vaccination of macaques with DNA followed by adenoviral vectors encoding SIV gag alone delays infection by repeated mucosal challenge with SIV. AU - Almond,Neil, AU - Berry,Neil, AU - Stebbings,Richard, AU - Preston,Mark, AU - Ham,Claire, AU - Page,Mark, AU - Ferguson,Debbie, AU - Rose,Nicola, AU - Li,Bo, AU - Mee,Edward T, AU - Hassall,Mark, AU - Stahl-Hennig,Christiane, AU - Athanasopoulos,Takis, AU - Papagatsias,Timos, AU - Herath,Shanthi, AU - Benlahrech,Adel, AU - Dickson,George, AU - Meiser,Andrea, AU - Patterson,Steven, Y1 - 2019/08/14/ PY - 2019/8/16/entrez JF - Journal of virology JO - J. Virol. N2 - Vaccines aimed at inducing T cell responses to protect against human immunodeficiency virus (HIV) infection have been under development for more than 15 years. Replication defective adenovirus (rAd) vaccine vectors are at the forefront of this work and tested extensively in the simian immunodeficiency virus (SIV) challenge macaque model. Vaccination with rAd vectors coding for SIV gag or other non-envelope proteins induce T cell responses that control virus load but disappointingly are unsuccessful so far in preventing infection and attention has turned to inducing antibodies to the envelope. However, here we report that Mauritian cynomologus macaques, Macaca fascicularis (MCM), vaccinated against unmodified gag alone with a DNA prime followed by a rAd boost exhibit increased protection from infection by repeated intrarectal challenge with low dose SIVmac251. There was no evidence of infection followed by eradication. A significant correlation was observed between cytokine expression by CD4 T cells and delayed infection. Vaccination with gag fused to the ubiquitin gene or fragmented, designed to increase CD8 magnitude and breadth, did not confer resistance to challenge or enhance immunity. On infection a significant reduction in peak virus load was observed in all vaccinated animals including those vaccinated with modified gag These findings suggest that a non-persistent viral vector vaccine coding for internal virus proteins may be able to protect against HIV-1 infection. The mechanisms are probably distinct from antibody-mediated virus neutralization or cytotoxic CD8 cell killing of virus infected cells and may be mediated in part by CD4 T cells.IMPORTANCE The Simian Immunodeficiency Virus (SIV) macaque model represents the best animal model for testing new HIV-1 vaccines. Previous studies employing replication defective adenovirus (rAd) vectors that transiently express SIV internal proteins induced T cell responses that controlled virus load but did not protect against virus challenge. However, we show for the first time that SIV gag delivered in a DNA prime followed by a boost with rAd vector confers resistance to SIV intrarectal challenge. Other partially successful SIV/HIV-1 protective vaccines induce antibody to envelope and neutralise the virus or mediate antibody dependent cytotoxicity. Induction of CD8 T cells which do not prevent initial infection but eradicate infected cells before infection becomes established have also shown some success. By contrast the vaccine described here mediates resistance by a different mechanism from that described above which may reflect CD4 T cell activity. This could indicate an alternative approach for HIV-1 vaccine development. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/31413132/Vaccination_of_macaques_with_DNA_followed_by_adenoviral_vectors_encoding_SIV_gag_alone_delays_infection_by_repeated_mucosal_challenge_with_SIV L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=31413132 DB - PRIME DP - Unbound Medicine ER -