HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates.

Details

Serval ID
serval:BIB_93D42C1777C5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates.
Journal
Journal of virology
Author(s)
García-Arriaza J., Perdiguero B., Heeney J.L., Seaman M.S., Montefiori D.C., Yates N.L., Tomaras G.D., Ferrari G., Foulds K.E., Roederer M., Self S.G., Borate B., Gottardo R., Phogat S., Tartaglia J., Barnett S.W., Burke B., Cristillo A.D., Weiss D.E., Lee C., Kibler K.V., Jacobs B.L., Wagner R., Ding S., Pantaleo G., Esteban M.
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Publication state
Published
Issued date
01/05/2017
Peer-reviewed
Oui
Volume
91
Number
9
Pages
1-20
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4(+) and CD8(+) T cells, here we compared the HIV-1-specific immunogenicity elicited in nonhuman primates immunized with two replicating NYVAC vectors that have been modified by the insertion of the K1L and C7L vaccinia virus host range genes and express the clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC). Additionally, one NYVAC-C-KC vector was generated by deleting the viral gene B19R, an inhibitor of the type I interferon response (NYVAC-C-KC-ΔB19R). An immunization protocol mimicking that of the RV144 phase III clinical trial was used. Two groups of macaques received two doses of the corresponding NYVAC-C-KC vectors (weeks 0 and 4) and booster doses with NYVAC-C-KC vectors plus the clade C HIV-1 gp120 protein (weeks 12 and 24). The two replicating NYVAC-C-KC vectors induced enhanced and similar HIV-1-specific CD4(+) and CD8(+) T cell responses, similar levels of binding IgG antibodies, low levels of IgA antibodies, and high levels of antibody-dependent cellular cytotoxicity responses and HIV-1-neutralizing antibodies. Small differences within the NYVAC-C-KC-ΔB19R group were seen in the magnitude of CD4(+) and CD8(+) T cells, the induction of some cytokines, and the neutralization of some HIV-1 isolates. Thus, replication-competent NYVAC-C-KC vectors acquired relevant immunological properties as vaccine candidates against HIV/AIDS, and the viral B19 molecule exerts some control of immune functions.IMPORTANCE It is of special importance to find a safe and effective HIV/AIDS vaccine that can induce strong and broad T cell and humoral immune responses correlating with HIV-1 protection. Here we developed novel replicating poxvirus NYVAC-based HIV/AIDS vaccine candidates expressing clade C HIV-1 antigens, with one of them lacking the vaccinia virus B19 protein, an inhibitor of the type I interferon response. Immunization of nonhuman primates with these novel NYVAC-C-KC vectors and the protein component gp120 elicited high levels of T cell and humoral immune responses, with the vector containing a deletion in B19R inducing a trend toward a higher magnitude of CD4(+) and CD8(+) T cell responses and neutralization of some HIV-1 strains. These poxvirus vectors could be considered HIV/AIDS vaccine candidates based on their activation of potential immune correlates of protection.

Keywords
AIDS Vaccines/genetics, AIDS Vaccines/immunology, Animals, Antibodies, Neutralizing/blood, Antibodies, Neutralizing/immunology, Antibody-Dependent Cell Cytotoxicity/immunology, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/immunology, HIV Antibodies/blood, HIV Antibodies/immunology, HIV Antigens/immunology, HIV Envelope Protein gp120/immunology, HIV Infections/prevention & control, Interferon Type I/genetics, Macaca mulatta, Male, Receptors, Interferon/genetics, Receptors, Interferon/immunology, Vaccination, Vaccines, Virus-Like Particle/immunology, Vaccinia virus/genetics, env Gene Products, Human Immunodeficiency Virus/genetics, env Gene Products, Human Immunodeficiency Virus/metabolism
Pubmed
Open Access
Yes
Create date
16/02/2017 11:11
Last modification date
20/08/2019 15:56
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