Kanesa-Thasan N, Sun W, Ludwig G V, Rossi C, Putnak J R, Mangiafico J A, Innis B L, Edelman R
Walter Reed Army Institute of Research, Washington, District of Columbia, USA.
Am J Trop Med Hyg. 2003 Dec;69(6 Suppl):32-8. doi: 10.4269/ajtmh.2003.69.32.
Eight of 69 (12%) healthy adult volunteers vaccinated with monovalent live-attenuated dengue virus (DENV) vaccine candidates had atypical antibody responses, with depressed IgM:IgG antibody ratios and induction of high-titer hemagglutination-inhibiting and neutralizing (NT) antibodies to all four DENV serotypes. These features suggested flavivirus exposure prior to DENV vaccination, yet no volunteer had a history of previous flavivirus infection, flavivirus vaccination, or antibody to flaviviruses evident before DENV vaccination. Moreover, production of antibody to DENV by atypical responders (AR) was not accelerated compared with antibody responses in the 61 flavivirus-naive responders (NR). Further evaluation revealed no differences in sex, age, race, DENV vaccine candidate received, or clinical signs and symptoms following vaccination between AR and NR. However, viremia was delayed at the onset in AR compared with NR. A comparative panel of all AR and five randomly selected NR found flavivirus cross-reactive antibody after vaccination only in AR. Unexpectedly, six of eight AR had NT antibodies to yellow fever virus (YFV) > 1:10 before vaccination while NR had none (P = 0.04). The AR also universally demonstrated YFV NT antibody titers > or = 1:160 after DENV vaccination, whereas four of five NR failed to seroconvert (P = 0.02). Yellow fever virus priming broadens the antibody response to monovalent DENV vaccination. The effect of flavivirus priming on the clinical and immunologic response to tetravalent DENV vaccine remains to be determined.
69名接种单价减毒活登革病毒（DENV）候选疫苗的健康成年志愿者中，有8人（12%）出现非典型抗体反应，IgM:IgG抗体比值降低，并诱导产生了针对所有四种DENV血清型的高滴度血凝抑制和中和（NT）抗体。这些特征提示在接种DENV疫苗之前曾接触过黄病毒，但没有志愿者有既往黄病毒感染史、黄病毒疫苗接种史或在接种DENV疫苗之前有明显的黄病毒抗体。此外，与61名未接触过黄病毒的应答者（NR）的抗体反应相比，非典型应答者（AR）产生DENV抗体的速度并未加快。进一步评估发现，AR和NR在性别、年龄、种族、接种的DENV候选疫苗或接种后的临床体征和症状方面没有差异。然而，与NR相比，AR的病毒血症在发病时出现延迟。对所有AR和五名随机选择的NR进行的比较研究发现，仅在AR中接种疫苗后发现了黄病毒交叉反应抗体。出乎意料的是，8名AR中有6人在接种疫苗前对黄热病毒（YFV）的NT抗体>1:10，而NR中无人有此情况（P = 0.04）。AR在接种DENV疫苗后也普遍表现出YFV NT抗体滴度>或 = 1:160，而5名NR中有4人未能血清转化（P = 0.02）。黄热病毒预激发拓宽了对单价DENV疫苗的抗体反应。黄病毒预激发对四价DENV疫苗的临床和免疫反应的影响仍有待确定。
