Head-to-Head Comparison of Poxvirus NYVAC and ALVAC Vectors Expressing Identical HIV-1 Clade C Immunogens in Prime-Boost Combination with Env Protein in Nonhuman Primates

García-Arriaza, Juan; Perdiguero, Beatriz; Heeney, Jonathan L.; Seaman, Michael S.; Montefiori, David C.; LaBranche, Celia C.; Yates, Nicole L.; Shen, Xiaoying; Tomaras, Georgia D.; Ferrari, Guido; Foulds, Kathryn E.; McDermott, Adrian B.; Kao, Shu‐Fang; Hawkins, Natalie; Self, Steve; Yao, Jiansheng; Farrell, Patrick J.; Phogat, Sanjay; Tartaglia, Jim; Barnett, Susan W.; Burke, Brian; Cristillo, Anthony D.; Weiss, Deborah; Lee, Carter; Kibler, Karen V.; Jacobs, Bert; Asbach, Benedikt; Wagner, Ralf; Ding, Song; Pantaleo, Giuseppe; Esteban, Mariano

doi:10.1128/jvi.01265-15

Cited by 34 publications

(40 citation statements)

References 56 publications

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“…We previously described the generation and characterization of nonreplicating NYVAC vectors expressing clade C HIV-1 trimeric gp140 or Gag-Pol-Nef as a polyprotein processed into Gag-derived VLPs and their immune behavior in mice (24) and in NHPs (13). Since these vectors do not replicate in human cells, it was important to define whether novel replication-competent NYVAC-KC vectors could be more immunogenic as a function of higher levels of antigen expression during infection.…”

Section: Resultsmentioning

confidence: 99%

“…booster doses of the corresponding NYVAC-C-KC vectors in the upper right arm, while in the left arm, animals received booster immunization with a bivalent clade C gp120 protein (1:1 mixture of 50 g of 1086 gp120 and 50 g of TV1 gp120 proteins adjuvanted with MF59). Immunological monitoring of HIV-1-specific T and B cell immune responses induced by both groups was performed by using peripheral blood mononuclear cells (PBMCs), serum samples, or rectal mucosal samples isolated at weeks 0, 6, 14, 26, and 36 (at the beginning of the study; 2 weeks after the second, third, and fourth immunizations; and at the end of the study, respectively), according to analytical approaches similar to those described previously for NHPs (13) (Fig. 2B).…”

Section: Figmentioning

confidence: 99%

“…At the same time, these constructs maintained limited virus spread in tissues and an attenuated phenotype (26). Additionally, further improved NYVAC recombinant vectors expressing HIV-1 immunogens, such as HIV-1 clade C(ZM96) trimeric soluble gp140 or Gag(ZM96)-Pol-Nef(CN54) as Gag-derived virus-like particles (VLPs), have been shown to have an enhanced HIV-1-specific immunogenicity profile in mice (24) and nonhuman primates (NHPs) (10,13).…”

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confidence: 99%

“…Thus, in order to optimize the immunization protocol with NYVAC vectors expressing HIV-1 antigens, various approaches in NHPs have been evaluated, either comparing NYVAC to ALVAC (13) or combining NYVAC with DNA vectors (10), peptides (22), and dendritic cell targets (28), which have all demonstrated promising results.…”

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confidence: 99%

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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

García-Arriaza

Perdiguero

Heeney

et al. 2017

J Virol

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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 ϩ and CD8 ϩ 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 Gagderived 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 ϩ and CD8 ϩ 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 ϩ and CD8 ϩ T cells, the induction of some cytokines, and the neutralization

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Section: Resultsmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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

García-Arriaza

Perdiguero

Heeney

et al. 2017

J Virol

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“…1A. The seven HIV-1 NHP studies included a DNA and viral vector (NYVAC/ALVAC/MVA) as a prime or no-prime immunogen and Env gp120, gp140, or viral vector (Ad5/NYVAC [40]) as a boosting immunogen. The seven SIV NHP studies include either DNA or viral vector (MVA) as a prime immunogen and either Env protein (monomer or viral particles [25,26]) or viral vector (MVA [27] or Ad5 [28]) as a boosting immunogen.…”

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confidence: 99%

Vaccine-Induced Linear Epitope-Specific Antibodies to Simian Immunodeficiency Virus SIVmac239 Envelope Are Distinct from Those Induced to the Human Immunodeficiency Virus Type 1 Envelope in Nonhuman Primates

Shen

Duffy

Howington

et al. 2015

J Virol

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To evaluate antibody specificities induced by simian immunodeficiency virus (SIV) versus human immunodeficiency virus type 1 (HIV-1) envelope antigens in nonhuman primate (NHP), we profiled binding antibody responses to linear epitopes in NHP studies with HIV-1 or SIV immunogens. We found that, overall, HIV-1 Env IgG responses were dominated by V3, with the notable exception of the responses to the vaccine strain A244 Env that were dominated by V2, whereas the anti-SIVmac239 Env responses were dominated by V2 regardless of the vaccine regimen.

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Application of area scaling analysis to identify natural killer cell and monocyte involvement in the GranToxiLux antibody dependent cell‐mediated cytotoxicity assay

et al. 2018

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Several different assay methodologies have been described for the evaluation of HIV or SIV‐specific antibody‐dependent cell‐mediated cytotoxicity (ADCC). Commonly used assays measure ADCC by evaluating effector cell functions, or by detecting elimination of target cells. Signaling through Fc receptors, cellular activation, cytotoxic granule exocytosis, or accumulation of cytolytic and immune signaling factors have been used to evaluate ADCC at the level of the effector cells. Alternatively, assays that measure killing or loss of target cells provide a direct assessment of the specific killing activity of antibodies capable of ADCC. Thus, each of these two distinct types of assays provides information on only one of the critical components of an ADCC event; either the effector cells involved, or the resulting effect on the target cell. We have developed a simple modification of our previously described high‐throughput ADCC GranToxiLux (GTL) assay that uses area scaling analysis (ASA) to facilitate simultaneous quantification of ADCC activity at the target cell level, and assessment of the contribution of natural killer cells and monocytes to the total observed ADCC activity when whole human peripheral blood mononuclear cells are used as a source of effector cells. The modified analysis method requires no additional reagents and can, therefore, be easily included in prospective studies. Moreover, ASA can also often be applied to pre‐existing ADCC‐GTL datasets. Thus, incorporation of ASA to the ADCC‐GTL assay provides an ancillary assessment of the ability of natural and vaccine‐induced antibodies to recruit natural killer cells as well as monocytes against HIV or SIV; or to any other field of research for which this assay is applied. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC.

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Head-to-Head Comparison of Poxvirus NYVAC and ALVAC Vectors Expressing Identical HIV-1 Clade C Immunogens in Prime-Boost Combination with Env Protein in Nonhuman Primates

Cited by 34 publications

References 56 publications

Vaccine-Induced Linear Epitope-Specific Antibodies to Simian Immunodeficiency Virus SIVmac239 Envelope Are Distinct from Those Induced to the Human Immunodeficiency Virus Type 1 Envelope in Nonhuman Primates

Application of area scaling analysis to identify natural killer cell and monocyte involvement in the GranToxiLux antibody dependent cell‐mediated cytotoxicity assay

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