從1998年大流行後，腸病毒71型（EV71）儼然成為台灣的地方性流行病，但對於該病毒的流行模式目前仍然不清楚。臨床觀察發現，EV71感染所造成輕重症之差異，似乎與是否感染其他腸病毒的病史有關。在我們研究中，已經證實EV71和克沙奇A16病毒（CA16）之間的確存在免疫交叉作用，並且在動物感染實驗證實此免疫交叉反應可保護小鼠，避免EV71強毒株感染引起的嚴重症狀。然而，在台灣還有許多其他腸病毒和EV71共同循環傳播（co-circulation），因此我們假設：先前其他非EV71腸病毒所引起的免疫力可能會影響EV71的流行。根據流行病學資料，我們選擇近年常有病例發生的CA4、CA16、CA24、克沙奇病毒B2（CB2）、伊科病毒9（E9）以及小兒麻痺病毒第2型（PV2）去探討他們與EV71之間的交互作用。首先，我們發現不同腸病毒在相同免疫條件下，引起的特異性細胞和體液免疫能力各有不同。在細胞免疫交互作用方面，以上六種腸病毒免疫母鼠的脾臟細胞，在EV71病毒抗原刺激下並不引起強烈的細胞增生，IFN-產量亦不明顯。在體液免疫交叉作用方面，CA16和CA24免疫血清中含有能辨識EV71病毒抗原交叉作用的抗體。此外，CA16、CA24和E9免疫血清能延緩EV71感染引起的細胞病變。根據以上結果，我們推測CA16、CA24和E9與EV71之間可能存在免疫交互作用，而CA4、CB2、E9、PV2則無，至於CA16、CA24、E9與EV71之間的免疫交互作用是否影響EV71之流行尚需進一步釐清。此外，本研究中發現與EV71同屬人類腸病毒A群（HEV-A）的CA4和EV71之間並無明顯交互作用，推測CA16與EV71存在的交互作用可能是特殊情況，並非都能套用在所有的HEV-A腸病毒。藉由了解不同腸病毒在族群中的免疫特性，以及與EV71之交叉反應，將有助於建構解釋EV71流行的合理模式，以作為預測流行之依據。

Enterovirus 71 (EV71) has become an endemic in Taiwan since the 1998 outbreaks. However, the circulation pattern of EV71 is poorly understood. Our previous studies demonstrated that there was a cross-reactivity between EV71 and Coxsackie A16 virus (CA16), which could provide a partial protection for EV71 infection in a mouse model. Thus, we hypothesize that the pre-existing intratypic and intertypic immunities may influence the prevalence of EV71. Based on epidemiological data, we have selected several non-EV71 enteroviruses including Poliovirus 2 (PV2), CA16, CA4, Coxsackie B2 virus (CB2), Echovirus 9（E9）, and CA24 virus to explore the extent of intertypic cross-reactivity among the enteroviruses. The developments of enterovirus specific T-cell and antibody responses were examined in the virus-immunized BALB/c mice. The results showed that different enterovirus induced varied degree of specific cellular and humoral immunity under the same immunization condition. Splenocytes from CA4-, CA16-, CA24-, CB2-, E9- and PV2-immunized mice proliferated slightly and had low IFN- production upon in vitro EV71 antigen stimulation. In addition, only CA16 and CA24 immune serum contained antibodies that could bind EV71 antigens by ELISA-based assay. Furthermore, CA16, CA24 and E9 immune serum could not neutralize EV71 but could delay its cytopathic effect. These results illustrated that the immunity induced by CA16, CA24 and E9 could cross react, more or less, with EV71. A better understanding of the immune status induced by different enteroviruses and its reactivity to EV71 would assist us to explain the circulation pattern of the virus.

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