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GMMA作为一种针对A群糖缀合物疫苗的替代载体

GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A .

作者信息

Palmieri Elena, Kis Zoltán, Ozanne James, Di Benedetto Roberta, Ricchetti Beatrice, Massai Luisa, Carducci Martina, Oldrini Davide, Gasperini Gianmarco, Aruta Maria Grazia, Rossi Omar, Kontoravdi Cleo, Shah Nilay, Mawas Fatme, Micoli Francesca

机构信息

GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy.

The Sargent Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.

出版信息

Vaccines (Basel). 2022 Jun 28;10(7):1034. doi: 10.3390/vaccines10071034.

Abstract

Group A (GAS) causes about 500,000 annual deaths globally, and no vaccines are currently available. The Group A Carbohydrate (GAC), conserved across all GAS serotypes, conjugated to an appropriate carrier protein, represents a promising vaccine candidate. Here, we explored the possibility to use Generalized Modules for Membrane Antigens (GMMA) as an alternative carrier system for GAC, exploiting their intrinsic adjuvant properties. Immunogenicity of GAC-GMMA conjugate was evaluated in different animal species in comparison to GAC-CRM; and the two conjugates were also compared from a techno-economic point of view. GMMA proved to be a good alternative carrier for GAC, resulting in a higher immune response compared to CRM in different mice strains, as verified by ELISA and FACS analyses. Differently from CRM, GMMA induced significant levels of anti-GAC IgG titers in mice also in the absence of Alhydrogel. In rabbits, a difference in the immune response could not be appreciated; however, antibodies from GAC-GMMA-immunized animals showed higher affinity toward purified GAC antigen compared to those elicited by GAC-CRM. In addition, the GAC-GMMA production process proved to be more cost-effective, making this conjugate particularly attractive for low- and middle-income countries, where this pathogen has a huge burden.

摘要

A组链球菌(GAS)每年在全球导致约50万人死亡,目前尚无可用疫苗。A组碳水化合物(GAC)在所有GAS血清型中都保守,与合适的载体蛋白偶联后,是一种有前景的疫苗候选物。在此,我们探索了使用膜抗原通用模块(GMMA)作为GAC替代载体系统的可能性,利用其固有的佐剂特性。将GAC-GMMA偶联物与GAC-CRM相比,在不同动物物种中评估其免疫原性;并且还从技术经济角度对这两种偶联物进行了比较。GMMA被证明是GAC的良好替代载体,通过ELISA和FACS分析验证,与不同小鼠品系中的CRM相比,能产生更高的免疫反应。与CRM不同,即使在没有氢氧化铝凝胶的情况下,GMMA在小鼠中也能诱导出显著水平的抗GAC IgG滴度。在兔子中,无法看出免疫反应有差异;然而,与GAC-CRM诱导产生的抗体相比,GAC-GMMA免疫动物产生的抗体对纯化的GAC抗原显示出更高的亲和力。此外,GAC-GMMA的生产过程被证明更具成本效益,这使得这种偶联物对中低收入国家特别有吸引力,因为在这些国家这种病原体造成的负担巨大。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c69/9324507/e16ab38acd32/vaccines-10-01034-g001.jpg

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