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Inactivated yellow fever 17D vaccine: development and nonclinical safety, immunogenicity and protective activity.
Vaccine. 2010 May 14; 28(22):3827-40.V

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 beta-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.

Authors+Show Affiliations

Kleiner Perkins Caufield & Byers, 2750 Sand Hill Road, Menlo Park, CA 94025, USA. tmonath@kpcb.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20347059

Citation

Monath, Thomas P., et al. "Inactivated Yellow Fever 17D Vaccine: Development and Nonclinical Safety, Immunogenicity and Protective Activity." Vaccine, vol. 28, no. 22, 2010, pp. 3827-40.
Monath TP, Lee CK, Julander JG, et al. Inactivated yellow fever 17D vaccine: development and nonclinical safety, immunogenicity and protective activity. Vaccine. 2010;28(22):3827-40.
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), 3827-40. https://doi.org/10.1016/j.vaccine.2010.03.023
Monath TP, et al. Inactivated Yellow Fever 17D Vaccine: Development and Nonclinical Safety, Immunogenicity and Protective Activity. Vaccine. 2010 May 14;28(22):3827-40. PubMed PMID: 20347059.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inactivated yellow fever 17D vaccine: development and nonclinical safety, immunogenicity and protective activity. 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, Y1 - 2010/03/26/ PY - 2010/01/10/received PY - 2010/03/08/revised PY - 2010/03/10/accepted PY - 2010/3/30/entrez PY - 2010/3/30/pubmed PY - 2010/7/29/medline SP - 3827 EP - 40 JF - Vaccine JO - Vaccine VL - 28 IS - 22 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 beta-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. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/20347059/Inactivated_yellow_fever_17D_vaccine:_development_and_nonclinical_safety_immunogenicity_and_protective_activity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(10)00359-2 DB - PRIME DP - Unbound Medicine ER -