TY - JOUR
T1 - Inactivated yellow fever 17D vaccine
T2 - 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.
PY - 2010/5/14
Y1 - 2010/5/14
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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U2 - 10.1016/j.vaccine.2010.03.023
DO - 10.1016/j.vaccine.2010.03.023
M3 - Article
C2 - 20347059
AN - SCOPUS:77952322608
SN - 0264-410X
VL - 28
SP - 3827
EP - 3840
JO - Vaccine
JF - Vaccine
IS - 22
ER -