Evidence map›Paper›PMID 41090223›Full record

ArticleImmunity, inflammation and disease2025

Generalized Modules for Membrane Antigens (GMMA) Elicit Mild Local Reactogenicity After Intramuscular Injection in Absence of Aluminum Salt Adjuvant.

Raffaella Cecchi, Silvia Maccari, Renzo Alfini, Roberta Di Benedetto, Simona Gallorini, Elena Cartocci, Sara Marchi, Giacomo Romagnoli, Erika Bartolini, Francesca Micoli and 1 more

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Article in Immunity, inflammation and disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Raffaella CecchiGSK Vaccines, Siena, Italy.
Silvia MaccariGSK Vaccines, Siena, Italy.
Renzo AlfiniGSK Vaccines Institute for Global Health (GVGH), Siena, Italy.
Roberta Di BenedettoGSK Vaccines Institute for Global Health (GVGH), Siena, Italy.
Simona GalloriniGSK Vaccines, Siena, Italy.
Elena CartocciGSK Vaccines, Siena, Italy.
Sara MarchiGSK Vaccines, Siena, Italy.
Giacomo RomagnoliGSK Vaccines, Siena, Italy.
Erika BartoliniGSK Vaccines, Siena, Italy.
Francesca MicoliGSK Vaccines Institute for Global Health (GVGH), Siena, Italy.
Diego PiccioliGSK Vaccines, Siena, Italy.

Funding

This work was sponsored by GlaxoSmithKline Biologicals SA which was involved in all stages of the study conduct and analysis.
6 · The paper itself

Abstract

BACKGROUND AND

objectivesGeneralized modules for membrane antigens (GMMA) are outer membrane vesicles derived from gram-negative bacteria that can be used to design affordable subunit vaccines. GMMA are highly immunogenic and capable to induce an optimal antigen-specific humoral immune response both in animals and humans. Despite their potent immunogenicity, GMMA are usually formulated with aluminum salts (alum) to reduce their potential systemic reactogenicity. GMMA, in fact, contain agonists of toll-like receptor 4 (TLR4) and TLR2 that possess pro-inflammatory activity. The adsorption of GMMA onto alum is believed to reduce their systemic exposure. However, it has been found that GMMA formulated without alum did not induce concerning signs of systemic reactogenicity in the rabbit model. Here, we asked whether GMMA promote local reactogenicity.

methodsWe immunized mice intramuscularly with GMMA alone or adsorbed to alum and analyzed the injection site during 7 days after treatment.

resultsWe found that GMMA alone promoted only mild inflammation within the muscle, whereas the presence of alum induced severe muscle inflammation, as expected. Thus, in the mouse model, GMMA demonstrated to possess mild local reactogenic potential, while alum is confirmed a major driver of local reactogenicity.

conclusionOur results further support the idea to investigate the reactogenicity of GMMA formulated without alum in clinical studies.

Indexed as

Antigens, BacterialBacterial Outer Membrane ProteinsAdjuvants, ImmunologicAlum CompoundsAnimalsFemaleInjections, IntramuscularMiceToll-Like Receptor 4Adjuvants, ImmunologicAlum Compoundsaluminum sulfateAntigens, BacterialBacterial Outer Membrane ProteinsToll-Like Receptor 4alumGMMAhistopathologyinflammationinjection sitemusclereactogenicity

Identifiers

PMID41090223
PMCPMC12521871

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.