Erbs Gitte, Jakobsen Jeanne Toft, Schmidt Signe Tandrup, Christensen Dennis, Bailey Mick, Jungersen Gregers
Infectious Disease Immunology, Center for Vaccine Research, SSI, Copenhagen, Denmark.
Bristol Veterinary School, Langford House, University of Bristol, UK.
Vaccine. 2025 Feb 6;46:126672. doi: 10.1016/j.vaccine.2024.126672. Epub 2024 Dec 28.
Mucosal secretory IgA (SIgA) produced by subepithelial plasma cells in the lamina propria is the major antigen-specific defense mechanism against mucosal infections. We investigated if a retinoic acid (RA)-containing adjuvant in parenteral immunization, can induce vaccine-specific SIgA in the jejunal lumen in a dose-dependent manner in neonatal pigs immunized with a Chlamydia hybrid antigen. To accurately quantify SIgA responses in mucosal secretions, an antigen-specific ELISA method with secondary detection of porcine secretory component rather than IgA was developed. RA facilitated a stronger (or faster) IgG, IgA, IgM and SIgA response in serum after primary immunization, and a more than 10-fold significantly increased level of vaccine-specific SIgA in jejunum at termination 2 weeks after the secondary boost, whereas IgA or SIgA responses in bronchoalveolar lavage (BAL) were not significantly increased after immunization with RA. Analyses of different isotype responses to vaccination and different sampling sites, revealed significant correlations between IgG and IgA responses in serum, and between IgG in serum and jejunum, while IgA in jejunum was neither correlated with IgA in serum nor with IgG in jejunum. This is indicative of IgG in jejunum being primarily a transudate from serum, while IgA is not. Jejunum SIgA correlated significantly with jejunum IgA and with both serum SIgA and IgA. Our results thus support the use of SC-specific reagents for mucosal SIgA responses, although IgA reagents to a lesser extent also reflects local antibodies. Although the IgA and SIgA levels in BAL were not significantly different with or without RA, we observed a significant correlation of vaccine-specific SIgA in jejunum and BAL, indicating a level of commonality in the regulation of mucosal antibodies in gut and respiratory system. In conclusion, an adjuvant with high concentration of RA was shown to increase the local intestinal mucosal antibody response after parenteral immunization in pigs.
固有层中上皮下浆细胞产生的黏膜分泌型IgA（SIgA）是抵御黏膜感染的主要抗原特异性防御机制。我们研究了在新生仔猪用衣原体杂交抗原免疫时，非肠道免疫中含视黄酸（RA）的佐剂是否能以剂量依赖的方式在空肠腔中诱导疫苗特异性SIgA。为了准确量化黏膜分泌物中的SIgA反应，开发了一种以猪分泌成分而非IgA作为二级检测的抗原特异性ELISA方法。RA促进了初次免疫后血清中更强（或更快）的IgG、IgA、IgM和SIgA反应，并且在二次加强免疫2周后处死时，空肠中疫苗特异性SIgA水平显著增加了10倍以上，而用RA免疫后支气管肺泡灌洗（BAL）中的IgA或SIgA反应并未显著增加。对疫苗接种的不同同种型反应和不同采样部位的分析显示，血清中IgG和IgA反应之间以及血清IgG与空肠之间存在显著相关性，而空肠中的IgA与血清中的IgA以及空肠中的IgG均无相关性。这表明空肠中的IgG主要是血清渗出液，而IgA不是。空肠SIgA与空肠IgA以及血清SIgA和IgA均显著相关。因此，我们的结果支持使用针对分泌成分的特异性试剂来检测黏膜SIgA反应，尽管IgA试剂在较小程度上也能反映局部抗体。尽管有无RA时BAL中的IgA和SIgA水平无显著差异，但我们观察到空肠和BAL中疫苗特异性SIgA存在显著相关性，表明肠道和呼吸系统中黏膜抗体的调节存在一定程度的共性。总之，已证明高浓度RA佐剂可在猪非肠道免疫后增强局部肠道黏膜抗体反应。
