Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector

M. Giel-Moloney; M. Esteban; B. H. Oakes; M. Vaine; B. Asbach; R. Wagner; G. J. Mize; A. G. Spies; J. McElrath; M. Perreau; T. Roger; A. Ives; T. Calandra; D. Weiss; B. Perdiguero; K. V. Kibler; B. Jacobs; S. Ding; G. D. Tomaras; D. C. Montefiori; G. Ferrari; N. L. Yates; M. Roederer; S. F. Kao; K. E. Foulds; B. T. Mayer; C. Bennett; R. Gottardo; M. Parrington; J. Tartaglia; S. Phogat; G. Pantaleo; H. Kleanthous; K. V. Pugachev

doi:10.1038/s41598-019-56550-4

Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector

M. Giel-Moloney, M. Esteban, B. H. Oakes, M. Vaine, B. Asbach, R. Wagner, G. J. Mize, A. G. Spies, J. McElrath, M. Perreau, T. Roger, A. Ives, T. Calandra, D. Weiss, B. Perdiguero, K. V. Kibler, B. Jacobs, S. Ding, G. D. Tomaras, D. C. MontefioriG. Ferrari, N. L. Yates, M. Roederer, S. F. Kao, K. E. Foulds, B. T. Mayer, C. Bennett, R. Gottardo, M. Parrington, J. Tartaglia, S. Phogat, G. Pantaleo, H. Kleanthous, K. V. Pugachev

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Abstract

Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.

Original language	English (US)
Article number	20005
Journal	Scientific reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-56550-4
State	Published - Dec 1 2019

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Giel-Moloney, M., Esteban, M., Oakes, B. H., Vaine, M., Asbach, B., Wagner, R., Mize, G. J., Spies, A. G., McElrath, J., Perreau, M., Roger, T., Ives, A., Calandra, T., Weiss, D., Perdiguero, B., Kibler, K. V., Jacobs, B., Ding, S., Tomaras, G. D., ... Pugachev, K. V. (2019). Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector. Scientific reports, 9(1), Article 20005. https://doi.org/10.1038/s41598-019-56550-4

Giel-Moloney, M, Esteban, M, Oakes, BH, Vaine, M, Asbach, B, Wagner, R, Mize, GJ, Spies, AG, McElrath, J, Perreau, M, Roger, T, Ives, A, Calandra, T, Weiss, D, Perdiguero, B, Kibler, KV , Jacobs, B, Ding, S, Tomaras, GD, Montefiori, DC, Ferrari, G, Yates, NL, Roederer, M, Kao, SF, Foulds, KE, Mayer, BT, Bennett, C, Gottardo, R, Parrington, M, Tartaglia, J, Phogat, S, Pantaleo, G, Kleanthous, H & Pugachev, KV 2019, 'Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector', Scientific reports, vol. 9, no. 1, 20005. https://doi.org/10.1038/s41598-019-56550-4

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title = "Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector",

abstract = "Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.",

author = "M. Giel-Moloney and M. Esteban and Oakes, {B. H.} and M. Vaine and B. Asbach and R. Wagner and Mize, {G. J.} and Spies, {A. G.} and J. McElrath and M. Perreau and T. Roger and A. Ives and T. Calandra and D. Weiss and B. Perdiguero and Kibler, {K. V.} and B. Jacobs and S. Ding and Tomaras, {G. D.} and Montefiori, {D. C.} and G. Ferrari and Yates, {N. L.} and M. Roederer and Kao, {S. F.} and Foulds, {K. E.} and Mayer, {B. T.} and C. Bennett and R. Gottardo and M. Parrington and J. Tartaglia and S. Phogat and G. Pantaleo and H. Kleanthous and Pugachev, {K. V.}",

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doi = "10.1038/s41598-019-56550-4",

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T1 - Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector

AU - Giel-Moloney, M.

AU - Esteban, M.

AU - Oakes, B. H.

AU - Vaine, M.

AU - Asbach, B.

AU - Wagner, R.

AU - Mize, G. J.

AU - Spies, A. G.

AU - McElrath, J.

AU - Perreau, M.

AU - Roger, T.

AU - Ives, A.

AU - Calandra, T.

AU - Weiss, D.

AU - Perdiguero, B.

AU - Kibler, K. V.

AU - Jacobs, B.

AU - Ding, S.

AU - Tomaras, G. D.

AU - Montefiori, D. C.

AU - Ferrari, G.

AU - Yates, N. L.

AU - Roederer, M.

AU - Kao, S. F.

AU - Foulds, K. E.

AU - Mayer, B. T.

AU - Bennett, C.

AU - Gottardo, R.

AU - Parrington, M.

AU - Tartaglia, J.

AU - Phogat, S.

AU - Pantaleo, G.

AU - Kleanthous, H.

AU - Pugachev, K. V.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.

AB - Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.

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JF - Scientific reports

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Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector

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