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首页> 外文期刊>Journal of pharmaceutical sciences. >Development of a single-shot subunit vaccine for HIV-1. 5. programmable in vivo autoboost and long lasting neutralizing response.
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Development of a single-shot subunit vaccine for HIV-1. 5. programmable in vivo autoboost and long lasting neutralizing response.

机译：开发用于HIV-1的单次亚单位疫苗。 5.可编程的体内自动升压和持久的中和反应。

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The subunit vaccine for HIV-1, recombinant glycoprotein 120 (rgp120), was used as a model antigen to evaluate the potential for a pulsatile single immunization vaccine formulation consisting of poly(lactic-co-glycolic) acid (PLGA) microspheres. We designed rgp120 PLGA microsphere formulations that provide a pulse of rgp120 at 1 to 6 months (depending on the polymer) after administration, mimicking another immunization. In these studies, the in vitro pulse of rgp120 correlated well with the observed in vivo autoboost as measured by an increase in anti-gp120 antibodies in guinea pigs. The immune response to the rgp120 PLGA microsphere formulations was increased by adding the soluble form of the saponin-derived adjuvant, QS-21. The use of small microspheres, however, did not increase the humoral response to rgp120. A single immunization with rgp120 PLGA microspheres resuspended in soluble rgp120 and QS-21 elicited neutralizing antibody titers that were comparable to titers obtained from two immunizations of rgp120 and QS-21 at the same total dose. Administration of rgp120 PLGA microspheres in baboons resulted in high, long-lasting neutralizing antibody titers that were greater than repeated immunizations with soluble rgp120 and QS-21. These studies also indicated that a continuous release of QS-21 at the injection site may provide a greater immune response than a bolus injection. Overall, this work demonstrated that PLGA microsphere formulations may be designed to provide in vivo pulses of an antigen eliminating the need for repeated immunizations.
机译：HIV-1的亚单位疫苗重组糖蛋白120（rgp120）被用作模型抗原，以评估由聚乳酸-乙醇酸（PLGA）微球组成的脉冲式单次免疫疫苗制剂的潜力。我们设计了rgp120 PLGA微球制剂，可在给药后1到6个月（取决于聚合物）提供rgp120脉冲，模仿另一种免疫方法。在这些研究中，rgp120的体外脉冲与观察到的体内自动升压密切相关，如通过豚鼠中抗gp120抗体的增加所测量的。通过添加可溶形式的皂苷衍生佐剂QS-21，可以提高对rgp120 PLGA微球制剂的免疫反应。然而，使用小微球体并不会增加对rgp120的体液反应。用rgp120 PLGA微球进行的单次免疫重悬于可溶性rgp120和QS-21中，产生的中和抗体效价与在相同总剂量下两次rgp120和QS-21免疫获得的效价相当。在狒狒中施用rgp120 PLGA微球可产生高，持久的中和抗体滴度，该滴度大于用可溶性rgp120和QS-21的重复免疫。这些研究还表明，在注射部位连续释放QS-21可能比大剂量注射提供更大的免疫应答。总体而言，这项工作表明PLGA微球制剂可设计为提供体内抗原脉冲，从而消除了重复免疫的需要。

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