Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]

Publication Date:
2018-07-18
Publisher:
The American Society for Microbiology (ASM)
Print ISSN:
0022-538X
Electronic ISSN:
1098-5514
Topics:
Medicine
Published by:
http://www.asm.org/
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autor Singh, S., Ramirez-Salazar, E. G., Doueiri, R., Valentin, A., Rosati, M., Hu, X., Keele, B. F., Shen, X., Tomaras, G. D., Ferrari, G., La; Branche, C., Montefiori, D. C., Das, J., Alter, G., Trinh, H. V., Hamlin, C., Rao, M., Dayton, F., Bear, J., Chowdhury, B., Alicea, C., Lifson, J. D., Broderick, K. E., Sardesai, N. Y., Sivananthan, S. J., Fox, C. B., Reed, S. G., Venzon, D. J., Hirsch, V. M., Pavlakis, G. N., Felber, B. K.
beschreibung We developed a method of simultaneous vaccination with DNA and protein resulting in robust and durable cellular and humoral immune responses with efficient dissemination to mucosal sites and protection against simian immunodeficiency virus (SIV) infection. To further optimize the DNA-protein coimmunization regimen, we tested a SIV mac251 -based vaccine formulated with either of two Toll-like receptor 4 (TLR4) ligand-based liposomal adjuvant formulations (TLR4 plus TLR7 [TLR4+7] or TLR4 plus QS21 [TLR4+QS21]) in macaques. Although both vaccines induced humoral responses of similar magnitudes, they differed in their functional quality, including broader neutralizing activity and effector functions in the TLR4+7 group. Upon repeated heterologous SIV smE660 challenge, a trend of delayed viral acquisition was found in vaccinees compared to controls, which reached statistical significance in animals with the TRIM-5α-resistant (TRIM-5α R) allele. Vaccinees were preferentially infected by an SIV smE660 transmitted/founder virus carrying neutralization-resistant A/K mutations at residues 45 and 47 in Env, demonstrating a strong vaccine-induced sieve effect. In addition, the delay in virus acquisition directly correlated with SIV smE660 -specific neutralizing antibodies. The presence of mucosal V1V2 IgG binding antibodies correlated with a significantly decreased risk of virus acquisition in both TRIM-5α R and TRIM-5α-moderate/sensitive (TRIM-5α M/S) animals, although this vaccine effect was more prominent in animals with the TRIM-5α R allele. These data support the combined contribution of immune responses and genetic background to vaccine efficacy. Humoral responses targeting V2 and SIV-specific T cell responses correlated with viremia control. In conclusion, the combination of DNA and gp120 Env protein vaccine regimens using two different adjuvants induced durable and potent cellular and humoral responses contributing to a lower risk of infection by heterologous SIV challenge. IMPORTANCE An effective AIDS vaccine continues to be of paramount importance for the control of the pandemic, and it has been proven to be an elusive target. Vaccine efficacy trials and macaque challenge studies indicate that protection may be the result of combinations of many parameters. We show that a combination of DNA and protein vaccinations applied at the same time provides rapid and robust cellular and humoral immune responses and evidence for a reduced risk of infection. Vaccine-induced neutralizing antibodies and Env V2-specific antibodies at mucosal sites contribute to the delay of SIV smE660 acquisition, and genetic makeup (TRIM-5α) affects the effectiveness of the vaccine. These data are important for the design of better vaccines and may also affect other vaccine platforms.
citation_standardnr 6305737
datenlieferant ipn_articles
feed_id 2375
feed_publisher The American Society for Microbiology (ASM)
feed_publisher_url http://www.asm.org/
insertion_date 2018-07-18
journaleissn 1098-5514
journalissn 0022-538X
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Society for Microbiology (ASM)
quelle Journal of Virology
relation http://jvi.asm.org/cgi/content/short/92/15/e00281-18?rss=1
search_space articles
shingle_author_1 Singh, S., Ramirez-Salazar, E. G., Doueiri, R., Valentin, A., Rosati, M., Hu, X., Keele, B. F., Shen, X., Tomaras, G. D., Ferrari, G., La; Branche, C., Montefiori, D. C., Das, J., Alter, G., Trinh, H. V., Hamlin, C., Rao, M., Dayton, F., Bear, J., Chowdhury, B., Alicea, C., Lifson, J. D., Broderick, K. E., Sardesai, N. Y., Sivananthan, S. J., Fox, C. B., Reed, S. G., Venzon, D. J., Hirsch, V. M., Pavlakis, G. N., Felber, B. K.
shingle_author_2 Singh, S., Ramirez-Salazar, E. G., Doueiri, R., Valentin, A., Rosati, M., Hu, X., Keele, B. F., Shen, X., Tomaras, G. D., Ferrari, G., La; Branche, C., Montefiori, D. C., Das, J., Alter, G., Trinh, H. V., Hamlin, C., Rao, M., Dayton, F., Bear, J., Chowdhury, B., Alicea, C., Lifson, J. D., Broderick, K. E., Sardesai, N. Y., Sivananthan, S. J., Fox, C. B., Reed, S. G., Venzon, D. J., Hirsch, V. M., Pavlakis, G. N., Felber, B. K.
shingle_author_3 Singh, S., Ramirez-Salazar, E. G., Doueiri, R., Valentin, A., Rosati, M., Hu, X., Keele, B. F., Shen, X., Tomaras, G. D., Ferrari, G., La; Branche, C., Montefiori, D. C., Das, J., Alter, G., Trinh, H. V., Hamlin, C., Rao, M., Dayton, F., Bear, J., Chowdhury, B., Alicea, C., Lifson, J. D., Broderick, K. E., Sardesai, N. Y., Sivananthan, S. J., Fox, C. B., Reed, S. G., Venzon, D. J., Hirsch, V. M., Pavlakis, G. N., Felber, B. K.
shingle_author_4 Singh, S., Ramirez-Salazar, E. G., Doueiri, R., Valentin, A., Rosati, M., Hu, X., Keele, B. F., Shen, X., Tomaras, G. D., Ferrari, G., La; Branche, C., Montefiori, D. C., Das, J., Alter, G., Trinh, H. V., Hamlin, C., Rao, M., Dayton, F., Bear, J., Chowdhury, B., Alicea, C., Lifson, J. D., Broderick, K. E., Sardesai, N. Y., Sivananthan, S. J., Fox, C. B., Reed, S. G., Venzon, D. J., Hirsch, V. M., Pavlakis, G. N., Felber, B. K.
shingle_catch_all_1 Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]
We developed a method of simultaneous vaccination with DNA and protein resulting in robust and durable cellular and humoral immune responses with efficient dissemination to mucosal sites and protection against simian immunodeficiency virus (SIV) infection. To further optimize the DNA-protein coimmunization regimen, we tested a SIV mac251 -based vaccine formulated with either of two Toll-like receptor 4 (TLR4) ligand-based liposomal adjuvant formulations (TLR4 plus TLR7 [TLR4+7] or TLR4 plus QS21 [TLR4+QS21]) in macaques. Although both vaccines induced humoral responses of similar magnitudes, they differed in their functional quality, including broader neutralizing activity and effector functions in the TLR4+7 group. Upon repeated heterologous SIV smE660 challenge, a trend of delayed viral acquisition was found in vaccinees compared to controls, which reached statistical significance in animals with the TRIM-5α-resistant (TRIM-5α R) allele. Vaccinees were preferentially infected by an SIV smE660 transmitted/founder virus carrying neutralization-resistant A/K mutations at residues 45 and 47 in Env, demonstrating a strong vaccine-induced sieve effect. In addition, the delay in virus acquisition directly correlated with SIV smE660 -specific neutralizing antibodies. The presence of mucosal V1V2 IgG binding antibodies correlated with a significantly decreased risk of virus acquisition in both TRIM-5α R and TRIM-5α-moderate/sensitive (TRIM-5α M/S) animals, although this vaccine effect was more prominent in animals with the TRIM-5α R allele. These data support the combined contribution of immune responses and genetic background to vaccine efficacy. Humoral responses targeting V2 and SIV-specific T cell responses correlated with viremia control. In conclusion, the combination of DNA and gp120 Env protein vaccine regimens using two different adjuvants induced durable and potent cellular and humoral responses contributing to a lower risk of infection by heterologous SIV challenge. IMPORTANCE An effective AIDS vaccine continues to be of paramount importance for the control of the pandemic, and it has been proven to be an elusive target. Vaccine efficacy trials and macaque challenge studies indicate that protection may be the result of combinations of many parameters. We show that a combination of DNA and protein vaccinations applied at the same time provides rapid and robust cellular and humoral immune responses and evidence for a reduced risk of infection. Vaccine-induced neutralizing antibodies and Env V2-specific antibodies at mucosal sites contribute to the delay of SIV smE660 acquisition, and genetic makeup (TRIM-5α) affects the effectiveness of the vaccine. These data are important for the design of better vaccines and may also affect other vaccine platforms.
Singh, S., Ramirez-Salazar, E. G., Doueiri, R., Valentin, A., Rosati, M., Hu, X., Keele, B. F., Shen, X., Tomaras, G. D., Ferrari, G., La; Branche, C., Montefiori, D. C., Das, J., Alter, G., Trinh, H. V., Hamlin, C., Rao, M., Dayton, F., Bear, J., Chowdhury, B., Alicea, C., Lifson, J. D., Broderick, K. E., Sardesai, N. Y., Sivananthan, S. J., Fox, C. B., Reed, S. G., Venzon, D. J., Hirsch, V. M., Pavlakis, G. N., Felber, B. K.
The American Society for Microbiology (ASM)
0022-538X
0022538X
1098-5514
10985514
shingle_catch_all_2 Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]
We developed a method of simultaneous vaccination with DNA and protein resulting in robust and durable cellular and humoral immune responses with efficient dissemination to mucosal sites and protection against simian immunodeficiency virus (SIV) infection. To further optimize the DNA-protein coimmunization regimen, we tested a SIV mac251 -based vaccine formulated with either of two Toll-like receptor 4 (TLR4) ligand-based liposomal adjuvant formulations (TLR4 plus TLR7 [TLR4+7] or TLR4 plus QS21 [TLR4+QS21]) in macaques. Although both vaccines induced humoral responses of similar magnitudes, they differed in their functional quality, including broader neutralizing activity and effector functions in the TLR4+7 group. Upon repeated heterologous SIV smE660 challenge, a trend of delayed viral acquisition was found in vaccinees compared to controls, which reached statistical significance in animals with the TRIM-5α-resistant (TRIM-5α R) allele. Vaccinees were preferentially infected by an SIV smE660 transmitted/founder virus carrying neutralization-resistant A/K mutations at residues 45 and 47 in Env, demonstrating a strong vaccine-induced sieve effect. In addition, the delay in virus acquisition directly correlated with SIV smE660 -specific neutralizing antibodies. The presence of mucosal V1V2 IgG binding antibodies correlated with a significantly decreased risk of virus acquisition in both TRIM-5α R and TRIM-5α-moderate/sensitive (TRIM-5α M/S) animals, although this vaccine effect was more prominent in animals with the TRIM-5α R allele. These data support the combined contribution of immune responses and genetic background to vaccine efficacy. Humoral responses targeting V2 and SIV-specific T cell responses correlated with viremia control. In conclusion, the combination of DNA and gp120 Env protein vaccine regimens using two different adjuvants induced durable and potent cellular and humoral responses contributing to a lower risk of infection by heterologous SIV challenge. IMPORTANCE An effective AIDS vaccine continues to be of paramount importance for the control of the pandemic, and it has been proven to be an elusive target. Vaccine efficacy trials and macaque challenge studies indicate that protection may be the result of combinations of many parameters. We show that a combination of DNA and protein vaccinations applied at the same time provides rapid and robust cellular and humoral immune responses and evidence for a reduced risk of infection. Vaccine-induced neutralizing antibodies and Env V2-specific antibodies at mucosal sites contribute to the delay of SIV smE660 acquisition, and genetic makeup (TRIM-5α) affects the effectiveness of the vaccine. These data are important for the design of better vaccines and may also affect other vaccine platforms.
Singh, S., Ramirez-Salazar, E. G., Doueiri, R., Valentin, A., Rosati, M., Hu, X., Keele, B. F., Shen, X., Tomaras, G. D., Ferrari, G., La; Branche, C., Montefiori, D. C., Das, J., Alter, G., Trinh, H. V., Hamlin, C., Rao, M., Dayton, F., Bear, J., Chowdhury, B., Alicea, C., Lifson, J. D., Broderick, K. E., Sardesai, N. Y., Sivananthan, S. J., Fox, C. B., Reed, S. G., Venzon, D. J., Hirsch, V. M., Pavlakis, G. N., Felber, B. K.
The American Society for Microbiology (ASM)
0022-538X
0022538X
1098-5514
10985514
shingle_catch_all_3 Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]
We developed a method of simultaneous vaccination with DNA and protein resulting in robust and durable cellular and humoral immune responses with efficient dissemination to mucosal sites and protection against simian immunodeficiency virus (SIV) infection. To further optimize the DNA-protein coimmunization regimen, we tested a SIV mac251 -based vaccine formulated with either of two Toll-like receptor 4 (TLR4) ligand-based liposomal adjuvant formulations (TLR4 plus TLR7 [TLR4+7] or TLR4 plus QS21 [TLR4+QS21]) in macaques. Although both vaccines induced humoral responses of similar magnitudes, they differed in their functional quality, including broader neutralizing activity and effector functions in the TLR4+7 group. Upon repeated heterologous SIV smE660 challenge, a trend of delayed viral acquisition was found in vaccinees compared to controls, which reached statistical significance in animals with the TRIM-5α-resistant (TRIM-5α R) allele. Vaccinees were preferentially infected by an SIV smE660 transmitted/founder virus carrying neutralization-resistant A/K mutations at residues 45 and 47 in Env, demonstrating a strong vaccine-induced sieve effect. In addition, the delay in virus acquisition directly correlated with SIV smE660 -specific neutralizing antibodies. The presence of mucosal V1V2 IgG binding antibodies correlated with a significantly decreased risk of virus acquisition in both TRIM-5α R and TRIM-5α-moderate/sensitive (TRIM-5α M/S) animals, although this vaccine effect was more prominent in animals with the TRIM-5α R allele. These data support the combined contribution of immune responses and genetic background to vaccine efficacy. Humoral responses targeting V2 and SIV-specific T cell responses correlated with viremia control. In conclusion, the combination of DNA and gp120 Env protein vaccine regimens using two different adjuvants induced durable and potent cellular and humoral responses contributing to a lower risk of infection by heterologous SIV challenge. IMPORTANCE An effective AIDS vaccine continues to be of paramount importance for the control of the pandemic, and it has been proven to be an elusive target. Vaccine efficacy trials and macaque challenge studies indicate that protection may be the result of combinations of many parameters. We show that a combination of DNA and protein vaccinations applied at the same time provides rapid and robust cellular and humoral immune responses and evidence for a reduced risk of infection. Vaccine-induced neutralizing antibodies and Env V2-specific antibodies at mucosal sites contribute to the delay of SIV smE660 acquisition, and genetic makeup (TRIM-5α) affects the effectiveness of the vaccine. These data are important for the design of better vaccines and may also affect other vaccine platforms.
Singh, S., Ramirez-Salazar, E. G., Doueiri, R., Valentin, A., Rosati, M., Hu, X., Keele, B. F., Shen, X., Tomaras, G. D., Ferrari, G., La; Branche, C., Montefiori, D. C., Das, J., Alter, G., Trinh, H. V., Hamlin, C., Rao, M., Dayton, F., Bear, J., Chowdhury, B., Alicea, C., Lifson, J. D., Broderick, K. E., Sardesai, N. Y., Sivananthan, S. J., Fox, C. B., Reed, S. G., Venzon, D. J., Hirsch, V. M., Pavlakis, G. N., Felber, B. K.
The American Society for Microbiology (ASM)
0022-538X
0022538X
1098-5514
10985514
shingle_catch_all_4 Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]
We developed a method of simultaneous vaccination with DNA and protein resulting in robust and durable cellular and humoral immune responses with efficient dissemination to mucosal sites and protection against simian immunodeficiency virus (SIV) infection. To further optimize the DNA-protein coimmunization regimen, we tested a SIV mac251 -based vaccine formulated with either of two Toll-like receptor 4 (TLR4) ligand-based liposomal adjuvant formulations (TLR4 plus TLR7 [TLR4+7] or TLR4 plus QS21 [TLR4+QS21]) in macaques. Although both vaccines induced humoral responses of similar magnitudes, they differed in their functional quality, including broader neutralizing activity and effector functions in the TLR4+7 group. Upon repeated heterologous SIV smE660 challenge, a trend of delayed viral acquisition was found in vaccinees compared to controls, which reached statistical significance in animals with the TRIM-5α-resistant (TRIM-5α R) allele. Vaccinees were preferentially infected by an SIV smE660 transmitted/founder virus carrying neutralization-resistant A/K mutations at residues 45 and 47 in Env, demonstrating a strong vaccine-induced sieve effect. In addition, the delay in virus acquisition directly correlated with SIV smE660 -specific neutralizing antibodies. The presence of mucosal V1V2 IgG binding antibodies correlated with a significantly decreased risk of virus acquisition in both TRIM-5α R and TRIM-5α-moderate/sensitive (TRIM-5α M/S) animals, although this vaccine effect was more prominent in animals with the TRIM-5α R allele. These data support the combined contribution of immune responses and genetic background to vaccine efficacy. Humoral responses targeting V2 and SIV-specific T cell responses correlated with viremia control. In conclusion, the combination of DNA and gp120 Env protein vaccine regimens using two different adjuvants induced durable and potent cellular and humoral responses contributing to a lower risk of infection by heterologous SIV challenge. IMPORTANCE An effective AIDS vaccine continues to be of paramount importance for the control of the pandemic, and it has been proven to be an elusive target. Vaccine efficacy trials and macaque challenge studies indicate that protection may be the result of combinations of many parameters. We show that a combination of DNA and protein vaccinations applied at the same time provides rapid and robust cellular and humoral immune responses and evidence for a reduced risk of infection. Vaccine-induced neutralizing antibodies and Env V2-specific antibodies at mucosal sites contribute to the delay of SIV smE660 acquisition, and genetic makeup (TRIM-5α) affects the effectiveness of the vaccine. These data are important for the design of better vaccines and may also affect other vaccine platforms.
Singh, S., Ramirez-Salazar, E. G., Doueiri, R., Valentin, A., Rosati, M., Hu, X., Keele, B. F., Shen, X., Tomaras, G. D., Ferrari, G., La; Branche, C., Montefiori, D. C., Das, J., Alter, G., Trinh, H. V., Hamlin, C., Rao, M., Dayton, F., Bear, J., Chowdhury, B., Alicea, C., Lifson, J. D., Broderick, K. E., Sardesai, N. Y., Sivananthan, S. J., Fox, C. B., Reed, S. G., Venzon, D. J., Hirsch, V. M., Pavlakis, G. N., Felber, B. K.
The American Society for Microbiology (ASM)
0022-538X
0022538X
1098-5514
10985514
shingle_title_1 Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]
shingle_title_2 Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]
shingle_title_3 Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]
shingle_title_4 Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]
timestamp 2025-06-30T23:36:08.653Z
titel Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]
titel_suche Control of Heterologous Simian Immunodeficiency Virus SIVsmE660 Infection by DNA and Protein Coimmunization Regimens Combined with Different Toll-Like-Receptor-4-Based Adjuvants in Macaques [Vaccines and Antiviral Agents]
topic WW-YZ
uid ipn_articles_6305737