Hamster neogenin, a host-cell protein contained in a respiratory syncytial virus candidate vaccine, induces antibody responses in rabbits but not in clinical trial participants
| Autor: | Ilse Dieussaert, Marta Picciolato, Ann-Muriel Steff, Bruno André, Koen Maleux, Maria Key Prato, Laurence Fissette, Chanel Cadieux-Dion, Xavier Czeszak, Marc Louckx, Gaël de Lannoy, Walthère Dewé, Dominique Ingels |
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| Rok vydání: | 2020 |
| Předmět: |
vaccine candidate
viruses Placenta respiratory syncytial virus Antibodies Viral law.invention 0302 clinical medicine law Pregnancy Cricetinae Immunology and Allergy 030212 general & internal medicine Respiratory system chemistry.chemical_classification Chinese hamster ovary cell virus diseases respiratory system host cell protein Recombinant DNA Female Rabbits Research Article Research Paper Adult 030231 tropical medicine Immunology Hamster Nerve Tissue Proteins Receptors Cell Surface CHO Cells Respiratory Syncytial Virus Infections Biology Virus 03 medical and health sciences Cricetulus RSV-PreF Respiratory Syncytial Virus Vaccines fusion protein Animals Humans Pharmacology Neogenin Infant Newborn Membrane Proteins Fusion protein Virology Antibodies Neutralizing Chinese hamster ovary Immunization chemistry Respiratory Syncytial Virus Human Antibody Formation Glycoprotein Viral Fusion Proteins |
| Zdroj: | Human Vaccines & Immunotherapeutics article-version (VoR) Version of Record |
| ISSN: | 2164-554X |
| Popis: | A recombinant respiratory syncytial virus (RSV) fusion glycoprotein candidate vaccine (RSV-PreF) manufactured in Chinese hamster ovary cells was developed for immunization of pregnant women, to protect newborns against RSV disease through trans-placental antibody transfer. Traces of a host-cell protein, hamster neogenin (haNEO1), were identified in purified RSV-PreF antigen material. Given the high amino-acid sequence homology between haNEO1 and human neogenin (huNEO1), there was a risk that potential vaccine-induced anti-neogenin immunity could affect huNEO1 function in mother or fetus. Anti-huNEO1 IgGs were measured by enzyme-linked immunosorbent assay in sera from rabbits and trial participants (Phase 1 and 2 trials enrolling 128 men and 500 non-pregnant women, respectively; NCT01905215/NCT02360475) collected after immunization with RSV-PreF formulations containing different antigen doses with/without aluminum-hydroxide adjuvant. In rabbits, four injections administered at 14-day intervals induced huNEO1-specific IgG responses in an antigen-dose- and adjuvant-dependent manner, which plateaued in the highest-dose groups after three injections. In humans, no vaccination-induced anti-huNEO1 IgG responses were detected upon a single immunization, as the values in vaccine and control groups fluctuated around pre-vaccination levels up to 90/360 days post-vaccination. A minority of participants had anti-huNEO1 levels ≥ assay cutoff before vaccination, which did not increase post-vaccination. Thus, despite detecting vaccine-induced huNEO1-specific responses in rabbits, we found no evidence that the candidate vaccine had induced anti-huNEO1 immunity in human adults. The antigen purification process was nevertheless optimized, and haNEO1-reduced vaccines were used in a subsequent Phase 2 trial enrolling 400 non-pregnant women (NCT02956837), in which again no vaccine-induced anti-huNEO1 responses were detected. |
| Databáze: | OpenAIRE |
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