Historic observations suggest that survivors of smallpox maintained lifelong immunity and protection to subsequent infection compared to vaccinated individuals. Although protective immunity by vaccination using a related virus (vaccinia virus (VACV) strains) was the key for smallpox eradication, it does not uniformly provide long term, or lifelong protective immunity [1]. To determine differences in humoral immune responses, mice were inoculated with VACV either systemically, using intranasal inoculation (IN), or locally by an intradermal (ID) route. We hypothesized that sub-lethal IN infections may mimic systemic or naturally occurring infection and lead to an immunodominance reaction, in contrast to localized ID immunization. The results demonstrated systemic immunization through an IN route led to enhanced adaptive immunity to VACV-expressed protein targets both in magnitude and in diversity when compared to an ID route using a VACV protein microarray. In addition, cytokine responses, assessed using a Luminex® mouse cytokine multiplex kit, following IN infection was greater than that stemming from ID infection. Overall, the results suggest that the route of immunization (or infection) influences antibody responses. The greater magnitude and diversity of response in systemic infection provides indirect evidence for anecdotal observations made during the smallpox era that survivors maintain lifelong protection. These findings also suggest that systemic or disseminated host immune induction may result in a superior response, that may influence the magnitude of, as well as duration of protective responses.

历史观察表明，与接种疫苗的人相比，天花的幸存者保持终生免疫力并保护其免受随后的感染。尽管使用相关病毒（牛痘病毒（VACV）株）进行疫苗接种可产生保护性免疫，这是根除天花的关键，但它不能统一提供长期或终生的保护性免疫[1]。为了确定体液免疫反应的差异，使用鼻内接种（IN）全身或通过皮内（ID）途径全身接种VACV小鼠。我们假设亚致死性IN感染可模仿全身或自然发生的感染，并导致免疫显性反应，这与局部ID免疫相反。结果表明，与使用VACV蛋白微阵列的ID途径相比，通过IN途径进行的全身免疫导致增强的针对VACV表达的蛋白靶标的适应性免疫，无论是大小还是多样性。此外，IN感染后使用Luminex®小鼠细胞因子多重检测试剂盒评估的细胞因子应答要大于ID感染引起的应答。总体而言，结果表明免疫（或感染）途径会影响抗体反应。在全身感染中反应的更大幅度和多样性为天花时代幸存者保持终身保护提供了间接证据。这些发现还表明，系统性或分散性宿主免疫诱导可能会产生更好的反应，从而影响