Inactivated yellow fever 17D vaccine: Development and nonclinical safety, immunogenicity and protective activity

Thomas P. Monath; Cynthia K. Lee; Justin G. Julander; Alicja Brown; David W. Beasley; Douglas M. Watts; Edward Hayman; Patrick Guertin; Joseph Makowiecki; Joseph Crowell; Philip Levesque; Gavin C. Bowick; Merribeth Morin; Elizabeth Fowler; Dennis W. Trent

doi:10.1016/j.vaccine.2010.03.023

Inactivated yellow fever 17D vaccine: Development and nonclinical safety, immunogenicity and protective activity

Thomas P. Monath
, Cynthia K. Lee
, Justin G. Julander
, Alicja Brown
, David W. Beasley
, Douglas M. Watts
, Edward Hayman
, Patrick Guertin
, Joseph Makowiecki
, Joseph Crowell
, Philip Levesque
, Gavin C. Bowick
, Merribeth Morin
, Elizabeth Fowler
, Dennis W. Trent

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

90 Scopus citations

Abstract

In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age <9 months and >60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with β-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX^®, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX^® [geometric mean titer (GMT) 20,480 vs. 1940, respectively (P < 0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine or a single dose of YF-VAX^® were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated.

Original language	English (US)
Pages (from-to)	3827-3840
Number of pages	14
Journal	Vaccine
Volume	28
Issue number	22
DOIs	https://doi.org/10.1016/j.vaccine.2010.03.023
State	Published - May 14 2010

Keywords

Immune response
Inactivated vaccine
Yellow fever

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2010.03.023

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Monath, T. P., Lee, C. K., Julander, J. G., Brown, A., Beasley, D. W., Watts, D. M., Hayman, E., Guertin, P., Makowiecki, J., Crowell, J., Levesque, P., Bowick, G. C., Morin, M., Fowler, E., & Trent, D. W. (2010). Inactivated yellow fever 17D vaccine: Development and nonclinical safety, immunogenicity and protective activity. Vaccine, 28(22), 3827-3840. https://doi.org/10.1016/j.vaccine.2010.03.023

Monath, TP, Lee, CK, Julander, JG, Brown, A, Beasley, DW, Watts, DM, Hayman, E, Guertin, P, Makowiecki, J, Crowell, J, Levesque, P, Bowick, GC, Morin, M, Fowler, E & Trent, DW 2010, 'Inactivated yellow fever 17D vaccine: Development and nonclinical safety, immunogenicity and protective activity', Vaccine, vol. 28, no. 22, pp. 3827-3840. https://doi.org/10.1016/j.vaccine.2010.03.023

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title = "Inactivated yellow fever 17D vaccine: Development and nonclinical safety, immunogenicity and protective activity",

abstract = "In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64\%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age <9 months and >60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with β-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX{\textregistered}, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX{\textregistered} [geometric mean titer (GMT) 20,480 vs. 1940, respectively (P < 0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine or a single dose of YF-VAX{\textregistered} were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated.",

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AU - Monath, Thomas P.

AU - Lee, Cynthia K.

AU - Julander, Justin G.

AU - Brown, Alicja

AU - Beasley, David W.

AU - Watts, Douglas M.

AU - Hayman, Edward

AU - Guertin, Patrick

AU - Makowiecki, Joseph

AU - Crowell, Joseph

AU - Levesque, Philip

AU - Bowick, Gavin C.

AU - Morin, Merribeth

AU - Fowler, Elizabeth

AU - Trent, Dennis W.

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N2 - In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age <9 months and >60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with β-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX®, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX® [geometric mean titer (GMT) 20,480 vs. 1940, respectively (P < 0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine or a single dose of YF-VAX® were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated.

AB - In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age <9 months and >60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with β-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX®, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX® [geometric mean titer (GMT) 20,480 vs. 1940, respectively (P < 0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine or a single dose of YF-VAX® were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated.

KW - Immune response

KW - Inactivated vaccine

KW - Yellow fever

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EP - 3840

JO - Vaccine

JF - Vaccine

IS - 22

ER -

Inactivated yellow fever 17D vaccine: Development and nonclinical safety, immunogenicity and protective activity

Abstract

Keywords

ASJC Scopus subject areas

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