Serum Institute of India Pvt. Ltd., Pune, India.
CMAX Clinical Research Pty. Ltd., Adelaide, Australia.
Vaccine. 2023 Aug 31;41(38):5614-5621. doi: 10.1016/j.vaccine.2023.07.045. Epub 2023 Jul 31.
Dengue fever is an important public health problem, especially in Asia and South America. A tetravalent live attenuated dengue vaccine was manufactured in India after receipt of vaccine strains from NIAID, NIH, USA.
This was a Phase 1, double-blind, randomized, placebo-controlled study performed in 60 healthy adults of 18 to 45 years. Participants were randomized 2:1 to receive a single subcutaneous injection of either a tetravalent live attenuated dengue vaccine or placebo. Safety was assessed by unsolicited adverse events (AEs) and solicited reactions through 21 days after vaccination and serious adverse events (SAEs) through the entire study period of 180 days. Dengue viremia was assessed at baseline and on day 9, 11 and 13 post-vaccination using a plaque assay. Immunogenicity was assessed using the plaque reduction neutralization test (PRNT) assay using vaccine-matched wild virus serotypes (DENV 1, DENV 2, DENV 3 and DENV 4) at baseline and on 56-, 84- and 180-days post-vaccination. PRNT assay using circulating wild type DENV 1, DENV 2, DENV 3 and DENV 4 were done on day 1 and day 85 for a subset of 31 participants.
60 participants were randomized to receive dengue vaccine (n = 40) or placebo (n = 20). 23 participants (59 %) showed DENV vaccine viremia post- vaccination for any of the four serotypes with majority on day 9 and day 11. At baseline, all participants were naïve by dengue PRNT for all four serotypes in both the study groups except for four in the dengue vaccine group and two in the placebo group. On day 57, the GMTs of neutralizing antibodies ranged from 66.76 (95 % CI 36.63, 121.69) to 293.84 (95 % CI 192.25, 449.11) for all four serotypes in the dengue vaccine group. On day 181 though the titers declined, they still remained much higher than the baseline. The titers in the placebo group did not change after vaccination. Seroconversion through day 85 ranged from 79.5 % for DENV 1 to 100 % for DENV2 while in the placebo group, no participant showed seroconversion through day 85. Similar trends were noted when PRNT was done using wild DENV serotypes in both vaccine and placebo groups. Among solicited reactions, injection site erythema, rash, headache, fatigue, myalgia and arthralgia were reported more frequently in the vaccine group than placebo group. All solicited reactions were of grade 1 or grade 2 severity and completely resolved. One unrelated serious adverse event was reported in the vaccine group.
A single dose of dengue vaccine was safe and well tolerated in adults. The vaccine was highly immunogenic with trivalent or tetravalent seroconversion and seropositivity in most of the participants. The study was funded by Serum Institute of India Pvt. Ltd., Pune, India.
gov: NCT04035278.
登革热是一个重要的公共卫生问题，特别是在亚洲和南美洲。印度在收到美国国立卫生研究院下属的国家过敏和传染病研究所提供的疫苗株后，制造了一种四价减毒活疫苗。
这是一项在 60 名 18 至 45 岁健康成年人中进行的 1 期、双盲、随机、安慰剂对照研究。参与者按照 2:1 的比例随机接受单次皮下注射四价减毒活疫苗或安慰剂。通过 21 天的疫苗接种后未报告的不良反应（AE）和征集反应以及整个 180 天的研究期间的严重不良反应（SAE）来评估安全性。在基线时以及接种后第 9、11 和 13 天使用噬斑减少中和试验（PRNT）检测登革热病毒血症，使用疫苗匹配的野生病毒血清型（DENV 1、DENV 2、DENV 3 和 DENV 4）在基线和接种后第 56、84 和 180 天进行免疫原性评估。在第 1 天和第 85 天对 31 名参与者中的一部分进行了使用循环野生型 DENV 1、DENV 2、DENV 3 和 DENV 4 的 PRNT 检测。
60 名参与者被随机分配接受登革热疫苗（n=40）或安慰剂（n=20）。23 名参与者（59%）在接种任何四种血清型的疫苗后出现登革热病毒血症，大多数发生在第 9 天和第 11 天。在基线时，除了登革热疫苗组的 4 名和安慰剂组的 2 名参与者外，两组的所有参与者对所有四种血清型的登革热 PRNT 均为初次。在第 57 天，登革热疫苗组的中和抗体几何平均滴度（GMT）范围为 66.76（95%CI 36.63,121.69）至 293.84（95%CI 192.25,449.11），用于所有四种血清型。尽管在第 181 天滴度下降，但仍远高于基线。安慰剂组在接种后滴度没有变化。通过第 85 天的血清转化率范围为 DENV 1 的 79.5%至 DENV2 的 100%，而在安慰剂组中，直到第 85 天没有参与者显示血清转化率。在疫苗和安慰剂组中使用野生型 DENV 血清型进行 PRNT 时，也观察到了类似的趋势。在征集反应中，疫苗组比安慰剂组更频繁地报告注射部位红斑、皮疹、头痛、疲劳、肌痛和关节痛。所有征集反应均为 1 级或 2 级严重程度，完全缓解。疫苗组报告了 1 例与研究无关的严重不良事件。
单次接种登革热疫苗在成年人中是安全且耐受良好的。该疫苗具有高度的免疫原性，大多数参与者均产生了三价或四价血清转化率和血清阳性。该研究由印度血清研究所私营有限公司资助，位于印度浦那。
gov: NCT04035278。
