PREVAX: A Phase I Clinical Trial of an EGF-Based Vaccine in Moderate-to-Severe COPD Patients

EGFR has been suggested to contribute to COPD development and progression. Excessive ligand activation of the receptor leads to epithelial hyperproliferation and increased production of mucus, together with alterations in the primary cilia. The present study was designed to evaluate the safety and e...

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Published in:	Vaccines (Basel) Vol. 12; no. 8; p. 833
Main Authors:	Hernandez Reyes, Jenysbel de la C, Santos Morales, Orestes, Hernandez Moreno, Laura, Pino Alfonso, Pedro Pablo, Neninger Vinageras, Elia, Knigths Montalvo, Julia Lilliam, Aguilar Sosa, Aliuska, Gonzalez Morera, Amnely, Lorenzo-Luaces Alvárez, Patricia, Aguilar Venegas, Yadira, Troche Concepción, Mayelin, Medel Pérez, Loipa, Santiesteban González, Yanela, García Fernández, Lázara, Regueiro Rodríguez, Lorena, Macías Abrahan, Amparo, Labrada Mon, Mayrel, León Monzón, Kalet, Saavedra Hernández, Danay, Crombet Ramos, Tania
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 24-07-2024 MDPI
Subjects:	Antibodies Antibody response Avidity Chronic illnesses Chronic obstructive pulmonary disease Cilia Depletion EGF-based vaccine EGF-depleting immunotherapy Epidermal growth factor epidermal growth factor receptor Epidermal growth factor receptors Exhaustion Immunogenicity Immunoglobulins Kinases Lung cancer Lung diseases Membranes Patients Peptides Phosphatase Phosphorylation Proteins Respiratory function Smoking Vaccines United States > US EGF-based vaccine epidermal growth factor epidermal growth factor receptor EGF-depleting immunotherapy chronic obstructive pulmonary disease
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Summary:	EGFR has been suggested to contribute to COPD development and progression. Excessive ligand activation of the receptor leads to epithelial hyperproliferation and increased production of mucus, together with alterations in the primary cilia. The present study was designed to evaluate the safety and effect of depleting EGF in moderate-to-severe COPD patients, with an EGF-based vaccine. A phase I trial was conducted in subjects with moderate or severe COPD. The anti-EGF vaccine schedule consisted of 4 biweekly doses followed by 4 monthly boosters. The primary endpoint was the evaluation of the safety and immunogenicity of the vaccine, together with the change in FEV1 and physical function at week 24. Twenty-six patients with moderate or severe COPD were included in the trial. The vaccine was well tolerated and no serious related adverse events were reported. Ninety percent of the individuals developed a protective antibody response. The specific anti-EGF antibodies had high avidity and were able to inhibit EGFR phosphorylation. At the end of vaccination, serum EGF became undetectable. At week 24, there was a clinically significant improvement in lung function, with a mean change in trough FEV1 of 106 mL. Patients also increased their physical functioning. The EGF-based vaccine was immunogenic and provoked an EGF exhaustion in patients with moderate-to-severe COPD. Depleting EGF might result in a meaningful increase in FEV1, with good tolerability. The current results provide new avenues to treat chronic inflammatory lung diseases associated with EGFR aberrant signaling.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work and share first authorship.
ISSN:	2076-393X 2076-393X
DOI:	10.3390/vaccines12080833