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Immunogenicity and protective efficacy of a formalin-inactivated rotavirus vaccine combined with lipid adjuvants
Kari Johansen1, Ulf Schröder, Lennart Svensson
1Department of Virology, Swedish Institute for Infectious Disease Control, Karolinska Institute, S-171 82, Solna, Sweden. kari.johansen@smi.ki.se
Abstract:
The immunogenicity and protective efficacy of inactivated rotavirus vaccine administered intramuscularly with lipid adjuvants; MPL (monophosphoryl lipid A from Salmonella minnesota) or L3 (monooleate/lauric acid) was evaluated in an infant mouse model. Purified and formalin-inactivated rhesus rotavirus (I-RRV) combined with one of the adjuvants were administered to female balb/c mice at 0, 4 and 8 weeks. High serum IgG antibody titers developed in all vaccinated groups; I-RRV (GMT 45524+/-9819), I-RRV-MPL (GMT 190637+/-64250) and I-RRV-L3 (GMT 126266+/-27553). The formalin-inactivation procedure preserved neutralizing epitopes and elicited high neutralizing antibody titers; I-RRV (GMT 43053 S.E.M.+/-4189), I-RRV-MPL (GMT 66398 S.E.M.+/-20202) and I-RRV-L3 (GMT 60887 S.E.M.+/-10750). All offsprings to immunized dams were protected against clinical diarrhea upon oral challenge with RRV. The IgG1/IgG2a ratio was in all immunized groups approximately 1 suggesting development of a balanced Th1/Th2 response.
Insights
Inactivated rotavirus vaccines with lipid adjuvants (MPL or L3) demonstrated strong immunogenicity and protective efficacy in a mouse model. Offspring of immunized mothers were protected against rotavirus challenge, indicating vaccine effectiveness.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Rotavirus is a leading cause of severe diarrheal disease in infants globally.
- Development of effective rotavirus vaccines is crucial for public health.
- Lipid adjuvants can enhance vaccine immunogenicity and efficacy.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of an inactivated rhesus rotavirus (I-RRV) vaccine.
- To assess the impact of two lipid adjuvants, MPL (monophosphoryl lipid A) and L3 (monooleate/lauric acid), on vaccine performance.
- To determine the protective effect of maternal immunization on offspring.
Main Methods:
- Female balb/c mice were immunized intramuscularly with I-RRV alone or combined with MPL or L3 adjuvants at 0, 4, and 8 weeks.
- Serum IgG antibody titers and neutralizing antibody titers were measured.
- Offspring were orally challenged with RRV to assess protection against clinical diarrhea.
- The IgG1/IgG2a ratio was analyzed to evaluate the Th1/Th2 immune response.
Main Results:
- All vaccinated groups showed high serum IgG and neutralizing antibody titers.
- The I-RRV vaccine with MPL or L3 adjuvants elicited significantly higher antibody titers compared to I-RRV alone.
- Formalin inactivation preserved neutralizing epitopes on the rotavirus.
- All offspring born to immunized dams were protected against rotavirus-induced diarrhea.
- A balanced Th1/Th2 immune response was observed, indicated by an IgG1/IgG2a ratio of approximately 1.
Conclusions:
- Intramuscular administration of inactivated rotavirus vaccine with lipid adjuvants (MPL or L3) is highly immunogenic.
- The vaccine formulation confers protection to offspring via maternal immunization.
- The findings support the potential of this inactivated rotavirus vaccine candidate for further development.
