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Abstract：
Immaturity of the neonatal immune system contributes to increased susceptibility to infectious diseases and poor vaccine responses. Therefore, better strategies for early life vaccination are needed. Adjuvants can enhance the magnitude and duration of immune responses. In this study we assessed the effects of the adjuvants dmLT and mmCT and different immunization routes, subcutaneous (s.c.) and intranasal (i.n.), on neonatal immune response to a pneumococcal conjugate vaccine Pn1-CRM197. Pn1-specific antibody (Ab) levels of neonatal mice immunized with Pn1-CRM197 alone were low. The adjuvants enhanced IgG Ab responses up to 8 weeks after immunization, more after s.c. than i.n. immunization. On the contrary, i.n. immunization with either adjuvant enhanced serum and salivary IgA levels more than s.c. immunization. In addition, both dmLT and mmCT enhanced germinal center formation and accordingly, dmLT and mmCT enhanced the induction and persistence of Pn1-specific IgG+ Ab-secreting cells (ASCs) in spleen and bone marrow (BM), irrespective of the immunization route. Furthermore, i.n. immunization enhanced Pn1-specific IgA+ ASCs in BM more than s.c. immunizatiofimmu.2022.1078904n. However, a higher i.n. dose of the Pn1-CRM197 was needed to achieve IgG response comparable to that elicited by s.c. immunization with either adjuvant. We conclude that dmLT and mmCT enhance both induction and persistence of the neonatal immune response to the vaccine Pn1-CRM197, following mucosal or parenteral immunization. This indicates that dmLT and mmCT are promising adjuvants for developing safe and effective early life vaccination strategies.
摘要：
新生儿免疫系统的不成熟导致对传染病的易感性增加和疫苗应答差。因此,需要更好的早期疫苗接种策略。佐剂可以增强免疫应答的幅度和持续时间。在这项研究中，我们评估了佐剂dmLT和mmCT和不同免疫途径的作用，皮下（s.c.）和鼻内（i.n.），新生儿对肺炎球菌结合疫苗Pn1-CRM197的免疫反应。单独用Pn1-CRM197免疫的新生小鼠的Pn1特异性抗体(Ab)水平较低。佐剂在免疫后8周增强IgGAb应答，s.c.免疫后比i.n.免疫后更多。相反,i.n.与s.c.免疫相比,用任一佐剂免疫增强血清和唾液IgA水平。此外,dmLT和mmCT都增强了生发中心的形成，因此，dmLT和mmCT增强了脾和骨髓（BM）中Pn1特异性IgGAb分泌细胞（ASCs）的诱导和持久性，无论免疫途径如何。此外，i.n.免疫增强BM中的Pn1特异性IgA+ASCs比s.c.免疫接种2022.1078904n。然而,需要较高i.n.剂量的Pn1-CRM197来实现与用任一佐剂进行s.c.免疫所引发的IgG应答相当的IgG应答。我们得出的结论是，在粘膜或肠胃外免疫后，dmLT和mmCT增强了新生儿对疫苗Pn1-CRM197的免疫反应的诱导和持久性。这表明dmLT和mmCT是开发安全有效的生命早期疫苗接种策略的有前途的佐剂。
