Mancini Francesca, Caradonna Valentina, Alfini Renzo, Aruta Maria Grazia, Vitali Claudia Giorgina, Gasperini Gianmarco, Piccioli Diego, Berlanda Scorza Francesco, Rossi Omar, Micoli Francesca
GSK Vaccines Institute for Global Health S.r.l. (GVGH), 53100 Siena, Italy.
Dipartimento di Biotecnologie Mediche, Università degli Studi di Siena, 53100 Siena, Italy.
Pharmaceutics. 2024 Apr 22;16(4):568. doi: 10.3390/pharmaceutics16040568.
Shigellosis is one of the leading causes of diarrheal disease in low- and middle-income countries, particularly in young children, and is more often associated with antimicrobial resistance. Therefore, a preventive vaccine against shigellosis is an urgent medical need. We have proposed Generalised Modules for Membrane Antigens (GMMA) as an innovative delivery system for O-antigen, and an Alhydrogel formulation (1790GAHB) has been extensively tested in preclinical and clinical studies. Alhydrogel has been used as an adsorbent agent with the main purpose of reducing potential GMMA systemic reactogenicity. However, the immunogenicity and systemic reactogenicity of this GMMA-based vaccine formulated with or without Alhydrogel have never been compared. In this work, we investigated the potential adjuvant effect of aluminium salt-based adjuvants (Alhydrogel and AS37) on GMMA immunogenicity in mice and rabbits, and we found that GMMA alone resulted to be strongly immunogenic. The addition of neither Alhydrogel nor AS37 improved the magnitude or the functionality of vaccine-elicited antibodies. Interestingly, rabbits injected with either GMMA adsorbed on Alhydrogel or GMMA alone showed a limited and transient body temperature increase, returning to baseline values within 24 h after each vaccination. Overall, immunisation with unadsorbed GMMA did not raise any concern for animal health. We believe that these data support the clinical testing of GMMA formulated without Alhydrogel, which would allow for further simplification of GMMA-based vaccine manufacturing.
志贺氏菌病是低收入和中等收入国家腹泻病的主要病因之一，尤其是在幼儿中，并且更常与抗菌药物耐药性相关。因此，一种预防志贺氏菌病的疫苗是迫切的医学需求。我们已经提出了膜抗原通用模块（GMMA）作为O抗原的创新递送系统，并且一种氢氧化铝制剂（1790GAHB）已在临床前和临床研究中进行了广泛测试。氢氧化铝已被用作吸附剂，主要目的是降低潜在的GMMA全身反应原性。然而，这种含或不含氢氧化铝配制的基于GMMA的疫苗的免疫原性和全身反应原性从未被比较过。在这项工作中，我们研究了铝盐基佐剂（氢氧化铝和AS37）对小鼠和家兔GMMA免疫原性的潜在佐剂作用，并且我们发现单独的GMMA具有很强的免疫原性。添加氢氧化铝或AS37均未改善疫苗诱导抗体的强度或功能。有趣的是，注射吸附在氢氧化铝上的GMMA或单独注射GMMA的家兔体温升高有限且短暂，每次接种后24小时内恢复到基线值。总体而言，用未吸附的GMMA进行免疫对动物健康没有任何问题。我们相信这些数据支持对不含氢氧化铝配制的GMMA进行临床试验，这将允许进一步简化基于GMMA的疫苗生产。
