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An adjuvanted, tetravalent dengue virus purified inactivated vaccine candidate induces long-lasting and protective antibody responses against dengue challenge in rhesus macaques.

Fernandez S, Thomas SJ, De La Barrera R, Im-Erbsin R, Jarman RG, Baras B, Toussaint JF, Mossman S, Innis BL, Schmidt A, Malice MP, Festraets P, Warter L, Putnak JR, Eckels KH - Am. J. Trop. Med. Hyg. (2015)

Bottom Line: The immunogenicity and protective efficacy of a candidate tetravalent dengue virus purified inactivated vaccine (TDENV PIV) formulated with alum or an Adjuvant System (AS01, AS03 tested at three different dose levels, or AS04) was evaluated in a 0, 1-month vaccination schedule in rhesus macaques.One month after dose 2, all adjuvanted formulations elicited robust and persisting neutralizing antibody titers against all four dengue virus serotypes.This study shows that inactivated dengue vaccines, when formulated with alum or an Adjuvant System, are candidates for further development.

View Article: PubMed Central - PubMed

Affiliation: US Army Medical Component-Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand; Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland; GlaxoSmithKline Vaccines, Rixensart, Belgium; GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania.

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NAb responses to adjuvanted TDENV PIV formulations containing 0.5 μg antigen per serotype. NAb titers were measured by an ELISA-based MN50 assay in serum samples from monkeys who received two doses, 1 month apart, of either an adjuvanted TDENV PIV formulation (0.5 μg per serotype per dose), or PBS. Sera for the selected time points shown were obtained before (day 28) and 4, 12, 20, and 40 weeks after the second immunization (days 56, 168, and 308, respectively; N = 10 per group on days 28, 56, and 168 and N = 5 per group on day 308). The dashed line represents the cutoff value for a positive result. CI = confidence interval; D = day.
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Figure 2: NAb responses to adjuvanted TDENV PIV formulations containing 0.5 μg antigen per serotype. NAb titers were measured by an ELISA-based MN50 assay in serum samples from monkeys who received two doses, 1 month apart, of either an adjuvanted TDENV PIV formulation (0.5 μg per serotype per dose), or PBS. Sera for the selected time points shown were obtained before (day 28) and 4, 12, 20, and 40 weeks after the second immunization (days 56, 168, and 308, respectively; N = 10 per group on days 28, 56, and 168 and N = 5 per group on day 308). The dashed line represents the cutoff value for a positive result. CI = confidence interval; D = day.

Mentions: All vaccine groups exhibited seroconversion against each of the four DENV serotypes after the first dose (day 28), and GMTs peaked 1 month after the second dose on day 56. During the entire post-vaccination follow-up period, all groups were significantly different from the PBS group for all DENV serotypes (Figure 2). Although GMTs for each DENV serotype in all groups declined from day 56 to day 168, responses were persistent and remained remarkably stable between days 168 and 308. GMTs were comparable between the latter two time points (P > 0.05), except for the GMTs for DENV-3 in the AS03A, AS03B, and AS01E groups, which were higher on day 308 relative to day 168 (P < 0.05). Across time points and groups, GMTs against DENV-1 were significantly lower (P < 0.01) than those against DENV-2, -3, and -4 (GMR for DENV-1 compared with DENV-2, -3, and -4: 0.3–0.6). The GMTs for DENV-2, -3, and -4 were comparable at all time points, with the exception of relatively minor differences on day 28 (GMT for DENV-3 < GMTs for DENV-2 and -4; GMR = 0.7), day 168 (GMT for DENV-4 > GMT for DENV-2 and -3; GMR = 1.3), and day 252 (GMT for DENV-4 > GMT for DENV-2; GMR 1.4; P < 0.05).


An adjuvanted, tetravalent dengue virus purified inactivated vaccine candidate induces long-lasting and protective antibody responses against dengue challenge in rhesus macaques.

Fernandez S, Thomas SJ, De La Barrera R, Im-Erbsin R, Jarman RG, Baras B, Toussaint JF, Mossman S, Innis BL, Schmidt A, Malice MP, Festraets P, Warter L, Putnak JR, Eckels KH - Am. J. Trop. Med. Hyg. (2015)

NAb responses to adjuvanted TDENV PIV formulations containing 0.5 μg antigen per serotype. NAb titers were measured by an ELISA-based MN50 assay in serum samples from monkeys who received two doses, 1 month apart, of either an adjuvanted TDENV PIV formulation (0.5 μg per serotype per dose), or PBS. Sera for the selected time points shown were obtained before (day 28) and 4, 12, 20, and 40 weeks after the second immunization (days 56, 168, and 308, respectively; N = 10 per group on days 28, 56, and 168 and N = 5 per group on day 308). The dashed line represents the cutoff value for a positive result. CI = confidence interval; D = day.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385761&req=5

Figure 2: NAb responses to adjuvanted TDENV PIV formulations containing 0.5 μg antigen per serotype. NAb titers were measured by an ELISA-based MN50 assay in serum samples from monkeys who received two doses, 1 month apart, of either an adjuvanted TDENV PIV formulation (0.5 μg per serotype per dose), or PBS. Sera for the selected time points shown were obtained before (day 28) and 4, 12, 20, and 40 weeks after the second immunization (days 56, 168, and 308, respectively; N = 10 per group on days 28, 56, and 168 and N = 5 per group on day 308). The dashed line represents the cutoff value for a positive result. CI = confidence interval; D = day.
Mentions: All vaccine groups exhibited seroconversion against each of the four DENV serotypes after the first dose (day 28), and GMTs peaked 1 month after the second dose on day 56. During the entire post-vaccination follow-up period, all groups were significantly different from the PBS group for all DENV serotypes (Figure 2). Although GMTs for each DENV serotype in all groups declined from day 56 to day 168, responses were persistent and remained remarkably stable between days 168 and 308. GMTs were comparable between the latter two time points (P > 0.05), except for the GMTs for DENV-3 in the AS03A, AS03B, and AS01E groups, which were higher on day 308 relative to day 168 (P < 0.05). Across time points and groups, GMTs against DENV-1 were significantly lower (P < 0.01) than those against DENV-2, -3, and -4 (GMR for DENV-1 compared with DENV-2, -3, and -4: 0.3–0.6). The GMTs for DENV-2, -3, and -4 were comparable at all time points, with the exception of relatively minor differences on day 28 (GMT for DENV-3 < GMTs for DENV-2 and -4; GMR = 0.7), day 168 (GMT for DENV-4 > GMT for DENV-2 and -3; GMR = 1.3), and day 252 (GMT for DENV-4 > GMT for DENV-2; GMR 1.4; P < 0.05).

Bottom Line: The immunogenicity and protective efficacy of a candidate tetravalent dengue virus purified inactivated vaccine (TDENV PIV) formulated with alum or an Adjuvant System (AS01, AS03 tested at three different dose levels, or AS04) was evaluated in a 0, 1-month vaccination schedule in rhesus macaques.One month after dose 2, all adjuvanted formulations elicited robust and persisting neutralizing antibody titers against all four dengue virus serotypes.This study shows that inactivated dengue vaccines, when formulated with alum or an Adjuvant System, are candidates for further development.

View Article: PubMed Central - PubMed

Affiliation: US Army Medical Component-Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand; Walter Reed Army Institute of Research (WRAIR), Silver Spring, Maryland; GlaxoSmithKline Vaccines, Rixensart, Belgium; GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania.

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Related in: MedlinePlus