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Published on: June 25, 2015
Immunogenicity of a thermally inactivated rotavirus vaccine in mice
Baoming Jiang1, Yuhuan Wang, Jean-Francois Saluzzo
1Gastroenteritis and Respiratory Virus Laboratory Branch, Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. Baoming.Jiang@cdc.hhs.gov
Abstract:
Current approaches to the prevention of severe rotavirus diarrhea and deaths in children have all been through the use of live oral vaccines. To develop a safe and effective inactivated rotavirus vaccine (IRV), a new simple, rapid and robust method for the inactivation is critical and essential because chemical inactivation commonly used for a number of killed vaccines has been a challenge and problematic for rotavirus. We have examined an array of thermal conditions and demonstrated that purified YK-1 rotavirus in diluent buffer can be completely inactivated by heat treatment, as evidenced by the lack of virus growth in two successive passages in cell culture. Unlike chemical treatment that often causes physical and biochemical damages to viruses, thermally inactivated rotavirus particles maintained their structural, biochemical and antigenic integrity. A two-dose intramuscular administration of thermally inactivated YK-1 rotavirus without adjuvant resulted in high titers of total and neutralizing antibody in serum of mice. Adjuvant Al(OH)(3) further led to enhanced antibody titers and also dramatically lowered the amount of antigens in the vaccine formulation. Our results demonstrate the potential of heat inactivation as a novel approach to the manufacture of a safe and efficacious parenteral rotavirus vaccine, which should serve as an important addition to and back up for live oral rotavirus vaccine in children.
Insights
Heat inactivation offers a new method for creating a safe inactivated rotavirus vaccine (IRV). This thermal approach preserves rotavirus integrity and elicits a strong immune response, complementing existing live oral vaccines.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Current rotavirus diarrhea prevention relies on live oral vaccines.
- Developing a safe and effective inactivated rotavirus vaccine (IRV) requires a robust inactivation method.
- Chemical inactivation poses challenges for rotavirus due to potential damage.
Purpose of the Study:
- To investigate heat treatment as a novel inactivation method for rotavirus.
- To assess the structural, biochemical, and antigenic integrity of thermally inactivated rotavirus.
- To evaluate the immunogenicity of a parenteral inactivated rotavirus vaccine in mice.
Main Methods:
- Purified YK-1 rotavirus was subjected to various thermal conditions for inactivation.
- Inactivation was confirmed by assessing virus growth in cell culture (two passages).
- Thermally inactivated rotavirus was administered intramuscularly to mice, with and without Al(OH)(3) adjuvant, to measure antibody responses.
Main Results:
- Complete inactivation of YK-1 rotavirus was achieved through heat treatment.
- Thermally inactivated rotavirus particles retained their structural, biochemical, and antigenic integrity.
- Two doses of inactivated rotavirus vaccine induced high serum antibody titers in mice, enhanced by Al(OH)(3) adjuvant.
Conclusions:
- Heat inactivation is a viable and novel approach for producing safe and effective parenteral rotavirus vaccines.
- This method preserves viral integrity, unlike chemical inactivation.
- A thermally inactivated rotavirus vaccine could supplement live oral vaccines for children.
