Robust and balanced immune responses to all 4 dengue virus serotypes following administration of a single dose of a live attenuated tetravalent dengue vaccine to healthy, flavivirus-naive adults

Beth D. Kirkpatrick; Anna P. Durbin; Kristen K. Pierce; Marya P. Carmolli; Cecilia M. Tibery; Palmtama L. Grier; Noreen Hynes; Sean A. Diehl; Dan Elwood; Adrienne P. Jarvis; Beulah P. Sabundayo; Caroline E. Lyon; Catherine J. Larsson; Matthew Jo; Janece M. Lovchik; Catherine J. Luke; Mary C. Walsh; Ellen A. Fraser; Kanta Subbarao; Steven S. Whitehead

doi:10.1093/infdis/jiv082

Robust and balanced immune responses to all 4 dengue virus serotypes following administration of a single dose of a live attenuated tetravalent dengue vaccine to healthy, flavivirus-naive adults

Beth D. Kirkpatrick, Anna P. Durbin, Kristen K. Pierce, Marya P. Carmolli, Cecilia M. Tibery, Palmtama L. Grier, Noreen Hynes, Sean A. Diehl, Dan Elwood, Adrienne P. Jarvis, Beulah P. Sabundayo, Caroline E. Lyon, Catherine J. Larsson, Matthew Jo, Janece M. Lovchik, Catherine J. Luke, Mary C. Walsh, Ellen A. Fraser, Kanta Subbarao, Steven S. Whitehead

Research output: Contribution to journal › Article › peer-review

104 Scopus citations

Abstract

Background: The 4 serotypes of dengue virus, DENV-1-4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose. Methods: Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated. Results: A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose. Conclusions: A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic.

Original language	English (US)
Pages (from-to)	702-710
Number of pages	9
Journal	Journal of Infectious Diseases
Volume	212
Issue number	5
DOIs	https://doi.org/10.1093/infdis/jiv082
State	Published - Sep 1 2015

Keywords

Clinical trial
Dengue vaccine
Live attenuated tetravalent vaccine

ASJC Scopus subject areas

Immunology and Allergy
Infectious Diseases

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10.1093/infdis/jiv082

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Kirkpatrick, B. D., Durbin, A. P., Pierce, K. K., Carmolli, M. P., Tibery, C. M., Grier, P. L., Hynes, N., Diehl, S. A., Elwood, D., Jarvis, A. P., Sabundayo, B. P., Lyon, C. E., Larsson, C. J., Jo, M., Lovchik, J. M., Luke, C. J., Walsh, M. C., Fraser, E. A., Subbarao, K., & Whitehead, S. S. (2015). Robust and balanced immune responses to all 4 dengue virus serotypes following administration of a single dose of a live attenuated tetravalent dengue vaccine to healthy, flavivirus-naive adults. Journal of Infectious Diseases, 212(5), 702-710. https://doi.org/10.1093/infdis/jiv082

Robust and balanced immune responses to all 4 dengue virus serotypes following administration of a single dose of a live attenuated tetravalent dengue vaccine to healthy, flavivirus-naive adults. / Kirkpatrick, Beth D.; Durbin, Anna P.; Pierce, Kristen K. et al.
In: Journal of Infectious Diseases, Vol. 212, No. 5, 01.09.2015, p. 702-710.

Research output: Contribution to journal › Article › peer-review

Kirkpatrick, BD, Durbin, AP, Pierce, KK, Carmolli, MP, Tibery, CM, Grier, PL, Hynes, N, Diehl, SA, Elwood, D, Jarvis, AP, Sabundayo, BP, Lyon, CE, Larsson, CJ, Jo, M, Lovchik, JM, Luke, CJ, Walsh, MC, Fraser, EA, Subbarao, K & Whitehead, SS 2015, 'Robust and balanced immune responses to all 4 dengue virus serotypes following administration of a single dose of a live attenuated tetravalent dengue vaccine to healthy, flavivirus-naive adults', Journal of Infectious Diseases, vol. 212, no. 5, pp. 702-710. https://doi.org/10.1093/infdis/jiv082

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title = "Robust and balanced immune responses to all 4 dengue virus serotypes following administration of a single dose of a live attenuated tetravalent dengue vaccine to healthy, flavivirus-naive adults",

abstract = "Background: The 4 serotypes of dengue virus, DENV-1-4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose. Methods: Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated. Results: A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose. Conclusions: A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic.",

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author = "Kirkpatrick, {Beth D.} and Durbin, {Anna P.} and Pierce, {Kristen K.} and Carmolli, {Marya P.} and Tibery, {Cecilia M.} and Grier, {Palmtama L.} and Noreen Hynes and Diehl, {Sean A.} and Dan Elwood and Jarvis, {Adrienne P.} and Sabundayo, {Beulah P.} and Lyon, {Caroline E.} and Larsson, {Catherine J.} and Matthew Jo and Lovchik, {Janece M.} and Luke, {Catherine J.} and Walsh, {Mary C.} and Fraser, {Ellen A.} and Kanta Subbarao and Whitehead, {Steven S.}",

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AU - Durbin, Anna P.

AU - Pierce, Kristen K.

AU - Carmolli, Marya P.

AU - Tibery, Cecilia M.

AU - Grier, Palmtama L.

AU - Hynes, Noreen

AU - Diehl, Sean A.

AU - Elwood, Dan

AU - Jarvis, Adrienne P.

AU - Sabundayo, Beulah P.

AU - Lyon, Caroline E.

AU - Larsson, Catherine J.

AU - Jo, Matthew

AU - Lovchik, Janece M.

AU - Luke, Catherine J.

AU - Walsh, Mary C.

AU - Fraser, Ellen A.

AU - Subbarao, Kanta

AU - Whitehead, Steven S.

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N2 - Background: The 4 serotypes of dengue virus, DENV-1-4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose. Methods: Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated. Results: A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose. Conclusions: A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic.

AB - Background: The 4 serotypes of dengue virus, DENV-1-4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose. Methods: Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated. Results: A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose. Conclusions: A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic.

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Robust and balanced immune responses to all 4 dengue virus serotypes following administration of a single dose of a live attenuated tetravalent dengue vaccine to healthy, flavivirus-naive adults

Abstract

Keywords

ASJC Scopus subject areas

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