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Vaccine. 2019 Oct 17. pii: S0264-410X(19)31381-7. doi: 10.1016/j.vaccine.2019.10.018. [Epub ahead of print]

Novel calixarene-based surfactant enables low dose split inactivated vaccine protection against influenza infection.

Author information

1
CALIXAR, 60 Avenue Rockefeller 69008, Lyon, France.
2
Virologie et Pathologie Humaine-VirPath Team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.
3
Virologie et Pathologie Humaine-VirPath Team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France; VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon 69008, France.
4
Research Center in Infectious Diseases of the CHU de Quebec and Laval University, Quebec City, QC G1V 4G2, Canada.
5
Virologie et Pathologie Humaine-VirPath Team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France; Laboratoire de Virologie, Centre National de Référence des virus Influenza Sud, Institut des Agents Infectieux, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon F-69317, France.
6
Virologie et Pathologie Humaine-VirPath Team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France; VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon 69008, France. Electronic address: manuel.rosa-calatrava@univ-lyon1.fr.
7
CALIXAR, 60 Avenue Rockefeller 69008, Lyon, France. Electronic address: ajawhari@calixar.com.

Abstract

Influenza A viruses cause major morbidity and represent a severe global health problem. Current influenza vaccines are mainly egg-based products requiring the split of whole viruses using classical detergents such as Triton X-100, which implies certain limitations. Here, we report the use of the novel calixarene-based surfactant CALX133ACE as an alternative to classical detergents for influenza inactivated split vaccine preparation. We confirmed that CALX133ACE-based split HA antigens are fully functional and quantifiable by the "gold standard" method SRID. Additionally, as in the case of the Triton X-100-based split, the CALX133ACE-based split antigens are stable for at least 6 months at 4 °C. Moreover, immunization of mice with CALX133ACE-based split NYMC X-179A (H1N1) antigens harboring 10 to 30-fold less antigen than the commercialized trivalent inactivated vaccines Vaxigrip® or Fluviral® induced comparable efficient protection and neutralizing antibody responses against A(H1N1)pdm09 infection. Taken together, our results demonstrate for the first time the use of a calixarene-based detergent as an efficient splitting agent for the production of optimized influenza split antigens, paving the way for significant improvement in the vaccine manufacturing process, notably with regard to the current regulation on the prohibition of endocrine disruptors, such as Triton X-100.

KEYWORDS:

Calixarene; Detergent/surfactant; H1N1; Hemagglutinin; Immunization; Split inactivated influenza antigen; Triton

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