Publicaciones científicas

Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses

27-sep-2021 | Revista: Emerging Microbes & Infections

Belén Aparicio  1   2   3 , Noelia Casares  1   3 , Josune Egea  1   2   3 , Marta Ruiz  1   2   3 , Diana Llopiz  1   2   3 , Sheila Maestro  1   3 , Cristina Olagüe  1   3 , Gloria González-Aseguinolaza  1   3 , Cristian Smerdou  1   3 , Ascensión López-Díaz de Cerio  4 , Susana Inogés  4 , Felipe Prósper  4   5 , José R Yuste  4 , Francisco Carmona-Torre  4 , Gabriel Reina  4 , Juan J Lasarte  1   3 , Pablo Sarobe  1   2   3


Abstract

Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vaccine.

Epitope mapping using a panel of 10 amino acid overlapped 15-mer peptides covering region 401-515 from RBD did not identify linear epitopes when tested with sera from infected individuals or from RBD-immunized mice. However, immunization of mice with these 15-mer peptides identified four peptides located at region 446-480 that induced antibodies recognizing the peptides and RBD/S1 proteins.

Immunization with peptide 446-480 from S protein formulated with Freund's adjuvant or with CpG oligodeoxinucleotide/Alum induced polyepitopic antibody responses in BALB/c and C56BL/6J mice, recognizing RBD (titres of 3 × 104-3 × 105, depending on the adjuvant) and displaying neutralizing capacity (80-95% inhibition capacity; p < 0.05) against SARS-CoV-2. Murine CD4 and CD8T-cell epitopes were identified in region 446-480 and vaccination experiments using HLA transgenic mice suggested the presence of multiple human T-cell epitopes.

Antibodies induced by peptide 446-480 showed broad recognition of S proteins and S-derived peptides belonging to SARS-CoV-2 variants of concern. Importantly, vaccination with peptide 446-480 or with a cyclic version of peptide 446-488 containing a disulphide bridge between cysteines 480 and 488, protected humanized K18-hACE2 mice from a lethal dose of SARS-CoV-2 (62.5 and 75% of protection; p < 0.01 and p < 0.001, respectively). This region could be the basis for a peptide vaccine or other vaccine platforms against Covid-19.

CITA DEL ARTÍCULO  Emerg Microbes Infect. 2021 Dec;10(1):1931-1946.  doi: 10.1080/22221751.2021.1978823

Nuestros autores

Belén Aparicio de la Torre
Técnico de laboratorio del Programa de Inmunología e Inmunoterapia del Cima Universidad de Navarra
Josune Egea Urra
Marta Ruiz Egozcue
Técnico de Investigación Grupo de Investigación en Péptidos
Diana Llópiz Khatchikian
Cristina Olagüe Micheltorena