TY - JOUR
T1 - Vaccination of volunteers with low-dose, live-attenuated, dengue viruses leads to serotype-specific immunologic and virologic profiles
AU - Lindow, Janet C.
AU - Durbin, Anna P.
AU - Whitehead, Stephen S.
AU - Pierce, Kristen K.
AU - Carmolli, Marya P.
AU - Kirkpatrick, Beth D.
N1 - Funding Information:
This work was supported by contract HHSN272200900010C from the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Disease . We are grateful for the tireless efforts of the dengue vaccine teams. At the University of Vermont's Vaccine Testing Center we thank: Caroline Lyon, Catherine Larsson, Mary Claire Walsh, Ellen Fraser, Cassandra Ventrone, Elizabeth Dill, Nathan Borochoff-Porte, Stacia Rymarchyk, GCRC Staff, Donna Jacobs. At the Johns Hopkins Bloomberg School of Public Health, we thank: Cecilia Tibery, Donna Shaffer, Kawsar Talaat, Noreen Hynes, Beulah Sabundayo, Bridget McMahon, Janet Hurd, Kimberli Wanionek, and Sabrina Drayton. Lastly we wish to thank our biostatistician, Janice Y. Bunn, for her invaluable assistance.
PY - 2013/7/18
Y1 - 2013/7/18
N2 - There are currently no vaccines or therapeutics to prevent dengue disease which ranges in severity from asymptomatic infections to life-threatening illness. The National Institute of Allergy and Infectious Diseases (NIAID) Division of Intramural Research has developed live, attenuated vaccines to each of the four dengue serotypes (DENV-1-DENV-4). Two doses (10. PFU and 1000. PFU) of three monovalent vaccines were tested in human clinical trials to compare safety and immunogenicity profiles. DEN4δ30 had been tested previously at multiple doses. The three dengue vaccine candidates tested (DEN1δ30, DEN2/4δ30, and DEN3δ30/31) were very infectious, each with a human infectious dose 50%. ≤. 10. PFU. Further, infectivity rates ranged from 90 to 100% regardless of dose, excepting DEN2/4δ30 which dropped from 100% at the 1000. PFU dose to 60% at the 10. PFU dose. Mean geometric peak antibody titers did not differ significantly between doses for DEN1δ30 (92 ± 19 vs. 214 ± 97, p=. 0.08); however, significant differences were observed between the 10. PFU and 1000. PFU doses for DEN2/4δ30, 19 ± 9 vs. 102 ± 25 (p=. 0.001), and DEN3δ30/31, 119 ± 135 vs. 50 ± 50 (p=. 0.046). No differences in the incidences of rash, neutropenia, or viremia were observed between doses for any vaccines, though the mean peak titer of viremia for DEN1δ30 was higher at the 1000. PFU dose (0.5 ± 0 vs. 1.1 ± 0.1, p=. 0.007). These data demonstrate that a target dose of 1000. PFU for inclusion of each dengue serotype into a tetravalent vaccine is likely to be safe and generate a balanced immune response for all serotypes.
AB - There are currently no vaccines or therapeutics to prevent dengue disease which ranges in severity from asymptomatic infections to life-threatening illness. The National Institute of Allergy and Infectious Diseases (NIAID) Division of Intramural Research has developed live, attenuated vaccines to each of the four dengue serotypes (DENV-1-DENV-4). Two doses (10. PFU and 1000. PFU) of three monovalent vaccines were tested in human clinical trials to compare safety and immunogenicity profiles. DEN4δ30 had been tested previously at multiple doses. The three dengue vaccine candidates tested (DEN1δ30, DEN2/4δ30, and DEN3δ30/31) were very infectious, each with a human infectious dose 50%. ≤. 10. PFU. Further, infectivity rates ranged from 90 to 100% regardless of dose, excepting DEN2/4δ30 which dropped from 100% at the 1000. PFU dose to 60% at the 10. PFU dose. Mean geometric peak antibody titers did not differ significantly between doses for DEN1δ30 (92 ± 19 vs. 214 ± 97, p=. 0.08); however, significant differences were observed between the 10. PFU and 1000. PFU doses for DEN2/4δ30, 19 ± 9 vs. 102 ± 25 (p=. 0.001), and DEN3δ30/31, 119 ± 135 vs. 50 ± 50 (p=. 0.046). No differences in the incidences of rash, neutropenia, or viremia were observed between doses for any vaccines, though the mean peak titer of viremia for DEN1δ30 was higher at the 1000. PFU dose (0.5 ± 0 vs. 1.1 ± 0.1, p=. 0.007). These data demonstrate that a target dose of 1000. PFU for inclusion of each dengue serotype into a tetravalent vaccine is likely to be safe and generate a balanced immune response for all serotypes.
KW - Dengue vaccine
KW - Dengue virus
KW - HID
KW - Low dose
KW - Neutralizing antibodies
KW - Viremia
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U2 - 10.1016/j.vaccine.2013.05.075
DO - 10.1016/j.vaccine.2013.05.075
M3 - Article
C2 - 23735680
AN - SCOPUS:84879887698
SN - 0264-410X
VL - 31
SP - 3347
EP - 3352
JO - Vaccine
JF - Vaccine
IS - 33
ER -