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