On technological and immunological benefits of multivalent single-injection microsphere vaccines
On technological and immunological benefits of multivalent single-injection microsphere vaccines
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DOI：
10.1023/a:1020354809581
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发表时间：
2002-09-01
影响因子：
3.7
通讯作者：
Johansen, P
中科院分区：
文献类型：
--
作者：
Boehm, G;Peyre, M;Johansen, P
目的。为了开发单次注射的多价疫苗，我们研究了在生物可降解微球中结合抗原的可行性。此类疫苗有望通过减少产生免疫所需的接种次数来提高疫苗接种覆盖率。
方法。通过喷雾干燥法制备了聚乳酸和聚乳酸 - 羟基乙酸共聚物微球中的b型流感嗜血杆菌（Hib）结合物、白喉类毒素（DT）、破伤风类毒素（TT）和百日咳毒素（PT）的单价和多价疫苗，并研究了共包封的抗原和辅料对抗原负载量、释放和稳定性的影响。在豚鼠身上测试了两种四价制剂。
结果。单价Hib和PT疫苗在两种聚合物中的负载效率分别为10%（Hib）和30%（PT）。添加海藻糖时负载效率提高，当抗原以二价和三价组合共包封时提高得更多。含有共包封白蛋白的三价制剂（DT + PT + Hib）实现了最高负载效率（>80%）。在24小时孵育期间释放的抗原百分比通常为10 - 40%，并且随着负载效率的增加而降低。酶联免疫吸附测定（ELISA）数据显示，TT、DT和PT在整个包封和后续释放过程中保持抗原性。最后，由于在豚鼠中单次注射四价微球疫苗（DT + TT + PT + Hib）后引发了强烈且持续的抗体反应，所有抗原都保持了其免疫原性。
结论。本研究揭示了多价单次注射微球疫苗的技术优势以及免疫潜力。结果支持我们的假设，即几种抗原的共包封可能本质上改善抗原性和免疫原性抗原的包封，这可能是由于微包封过程中蛋白质浓度增加导致成分相互稳定。
Purpose. With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity.Methods. Mono- and multivalent vaccines of Haemophilus influenzae type b (Hib) conjugate, diphtheria toxoid (DT), tetanus toxoid (TT), and pertussis toxin (PT) in poly (lactic acid) and poly(lactic-coglycolic acid) microspheres were prepared by spray drying, and the influence of coencapsulated antigens and excipients on antigen loading, release, and stability was examined. Two tetravalent formulations were tested in guinea pigs.Results. Monovalent Hib and PT vaccines showed loading efficiencies of 10% (Hib) and 30% (PT) in both polymers. The loading efficiencies increased upon addition of trehalose and, even more, when the antigens were coencapsulated in di- and trivalent combinations. Highest loading efficiencies (>80%) were achieved with trivalent formulations (DT+PT+Hib) that also contained coencapsulated albumin. The percentage of antigen released during 24 h of incubation was typically 10-40% and decreased as loading efficiency increased. Enzyme-linked immunosorbent assay (ELISA) data revealed that TT, DT, and PT remained antigenic throughout the encapsulation and subsequent release processes. Finally, all antigens maintained their immunogenicity, since strong and sustained antibody responses were elicited after a single injection of tetravalent microsphere vaccines (DT+TT+PT+Hib) in guinea pigs.Conclusions. This study reveals technologic benefit as well as an immunological potential of multivalent single-injection microsphere vaccines. The results support our hypothesis that coencapsulation of several antigens may intrinsically improve entrapment of antigenic and immunogenic antigen probably by virtue of increased protein concentration during microencapsulation leading to mutual stabilization of the components.