有研究指出，不同型的腸病毒之間有交互作用，臨床的觀察也發現腸病毒71型 (EV71) 感染後是否會引起重症似乎與曾經感染其他腸病毒的病史有所關聯，因此我們假設：與其他腸病毒之間的交互作用會影響EV71的感染。由於克沙奇A16病毒 (CA16) 和EV71有部分共同的抗原性，因此我們針對CA16探討與EV71的交互作用。首先，我們發現CA16和EV71弱毒株經口服感染一日齡小鼠，可誘發小鼠產生中和效價為1:2和1:16的EV71特異抗體，此免疫反應可提高小鼠在EV71強毒株攻擊時的存活率；另外，利用成年小鼠製備的CA16及EV71免疫血清，在ELISA以及IFA的檢測中確實可以交互辨認兩種病毒，此外，CA16免疫血清對EV71呈現1:4的中和效價。在小鼠活體感染模式中，經CA16免疫血清被動免疫後，小鼠呈現較輕微的臨床症狀，組織中的病毒量較低，而且存活率較高。總括而言，CA16與EV71之間的免疫交互作用可能影響EV71的致病機制。

Previous studies suggest that there are intratypic as well as intertypic cross-reactions among enteroviruses. Therefore, we hypothesized that this cross-reaction may play a role in the pathogenesis of Enterovirus 71 (EV71) infection. Because other study showing that Coxsackie A16 virus (CA16) and EV71 shared same epitopes, we chose CA16 as the intertypic enterovirus to test our hypothesis. One-day-old mice orally immunized with either avirulent EV71 strain (4643) or CA16 developed antibodies against EV71 with neutralization titer of 1:16 and 1:2, respectively. Both EV71 avirulent strain (4643)- and CA16-immunized mice were more resistant to subsequent challenge by virulent EV71 strain (MP4). Hyperimmune serum (HI) against CA16 contained antibodies that could bind EV71 antigens in both ELISA-based and indirect immuno-fluorescence assays. Furthermore, CA16 HI could neutralize EV71 but not Coxsackie B3 virus or poliovirus at a titer of 1:4. Passive immunization with CA16 HI reduced the clinical score, diminished organ viral load and increased survival rate of mice after EV71 challenge. Splenocytes from CA16-immunized mice proliferated and produced IFN- upon EV71 or CA16, but not Coxsackie B3 antigen stimulation. These results illustrated that the immunity induced by CA16 indeed not only could cross react with EV71 but also offer partial protection against EV71. This intertypic reactivity of enteroviruses may play an important role in the pathogenesis of EV71.

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