Evidence map›Paper›PMID 40746548›Full record

ArticleFrontiers in immunology2025

Adjuvant combination and antigen multimerization shape neutralizing antibody and T cell responses to a SARS-CoV-2 RBD subunit vaccine.

João Pedro da Silva Nunes, Mariângela de Oliveira Silva, Juliana de Souza Apostolico, Isabela Pazotti Daher, Rodolfo Ferreira Marques, Marcio Massao Yamamoto, Alexia Adrianne Venceslau Brito Carvalho, Maria Fernanda de Castro-Amarante, Edison Luiz Durigon, Carsten Wrenger and 8 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

João Pedro da Silva NunesDepartamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil.
Mariângela de Oliveira SilvaDepartamento de Parasitologia, Universidade de São Paulo (USP), São Paulo, Brazil.
Juliana de Souza ApostolicoDepartamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil.
Isabela Pazotti DaherLaboratório de Imunologia, Instituto do Coração (InCor), Hospital das Clínicas- Faculdade de Medicina- Universidade de São Paulo (HCFMUSP), São Paulo, Brazil.
Rodolfo Ferreira MarquesDepartamento de Parasitologia, Universidade de São Paulo (USP), São Paulo, Brazil.
Marcio Massao YamamotoDepartamento de Parasitologia, Universidade de São Paulo (USP), São Paulo, Brazil.
Alexia Adrianne Venceslau Brito CarvalhoDepartamento de Parasitologia, Universidade de São Paulo (USP), São Paulo, Brazil.
Maria Fernanda de Castro-AmaranteDepartamento de Parasitologia, Universidade de São Paulo (USP), São Paulo, Brazil.
Edison Luiz DurigonDepartamento de Microbiologia, Universidade de São Paulo (USP), São Paulo, Brazil.
Carsten WrengerDepartamento de Parasitologia, Universidade de São Paulo (USP), São Paulo, Brazil.
Luiz Mario Ramos JaniniDepartamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil.
Edmarcia Elisa de SouzaDepartamento de Parasitologia, Universidade de São Paulo (USP), São Paulo, Brazil.
Robert Andreata-SantosDepartamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil.
Juliana Terzi MaricatoDepartamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil.
Edecio Cunha-NetoLaboratório de Imunologia, Instituto do Coração (InCor), Hospital das Clínicas- Faculdade de Medicina- Universidade de São Paulo (HCFMUSP), São Paulo, Brazil.
Jorge KalilLaboratório de Imunologia, Instituto do Coração (InCor), Hospital das Clínicas- Faculdade de Medicina- Universidade de São Paulo (HCFMUSP), São Paulo, Brazil.
Silvia Beatriz BoscardinDepartamento de Parasitologia, Universidade de São Paulo (USP), São Paulo, Brazil.
Daniela Santoro RosaDepartamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: The rapid development and deployment of multiple safe and effective COVID-19 vaccines were critical cornerstones of pandemic control. However, vaccine inequity and the emergence of new variants of concern (VOCs) highlighted major gaps in the global strategy to control SARS-CoV-2 infection. Despite the use of distinct platforms, most approved vaccines utilize the Spike protein as the main antigen due to its pivotal role in virus entry, mediated by the receptor binding domain (RBD). In this context, RBD stands out as a promising antigen for a subunit vaccine candidate, as it is the main target of neutralizing antibodies, has a well-established scalable production pipeline, and has proven safety. Approaches to enhance RBD immunogenicity encompass the addition of adjuvants and antigen multimerization. Methods: In this study, we compared the immunogenic properties of the Wuhan RBD monomer and homodimer with an RBD heterotrimer formulation composed of the Delta, Beta and Gamma variants. We also screened different adjuvants to optimize both humoral and cellular immunity. Results: Our results showed that immunization with the RBD dimer and trimer, in the presence of the adjuvant AddaS03, elicited a higher humoral response and a broader neutralization profile. Additionally, RBD-trimer immunization more efficiently inhibited viral replication in the lungs of mice challenged with the ancestral Wuhan strain compared to the monomer. We further optimized our vaccine formulation by combining the adjuvants AddaS03 and Poly I:C, which demonstrated a synergistic effect, integrating the potent humoral response induced by AddaS03 with the cellular Th1 skewing capacity of Poly I:C. The AddaS03+ Poly I:C mixture induced antibodies with higher affinity and an increased frequency of RBD-specific IgG2c-producing bone marrow plasma cells, highlighting the potential of this adjuvant combination to generate long-lived memory plasma cells. Additionally, we identified sequences within the RBD that induced specific IFNγ T cell responses. Peptide 12 (393-TNVYADSFVIRGDEVRQ-409) emerged as the immunodominant CD4 T cell epitope, whereas peptides 28 (505-YQPYRVVVLSFELLHAP-521) and 29 (512-VLSFELLHAPATVCGPK-528) successfully activated CD8 T cells. Conclusions: These findings underscore that antigen multimerization and the strategic combination of adjuvants can significantly improve vaccine immunogenicity.

Indexed as

Adjuvants, ImmunologicAntibodies, NeutralizingCOVID-19COVID-19 VaccinesSARS-CoV-2Spike Glycoprotein, CoronavirusT-LymphocytesAnimalsAntibodies, ViralFemaleHumansImmunity, CellularMiceMice, Inbred BALB CProtein MultimerizationVaccines, SubunitAdjuvants, ImmunologicAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Vaccines, SubunitadjuvantRBDrecombinant proteinSARS-CoV-2vaccine

Identifiers

PMID40746548
PMCPMC12310705

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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.