Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) enhances humoral immune responses against norovirus (GII.4) virus-like particles

Abstract

Objective To evaluate the immunopotentiating effect of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) as an adjuvant on norovirus (GⅡ.4) virus like particles (VLPs) in the development of norovirus vaccine. Methods BALB/c mice were intramuscularly immunized with norovirus (GⅡ.4) VLPs composed of capsid protein VP1 in combination with cGAMP or Al(OH)3. Norovirus VLPs-specific antibodies in serum were detected by ELISA. A synthetic histo-blood group antigen (HBGA)-VLPs blocking assay was used to analyze neutralizing antibodies against norovirus VLPs in serum samples. Results Immunization with norovirus VLPs in the presence of cGAMP induced a strong humoral immune response in BALB/c mice. Levels of specific IgG antibodies in serum induced by using cGAMP as the adjuvant were significantly higher than those induced by using Al(OH)3 adjuvant when immunization of BALB/c mice with the same dosage of VLPs. The antibody level induced by 1 μg of VLPs in combination with cGAMP was equivalent to that elicited by 10 μg of VLPs combined with Al(OH)3 adjuvant. Results of the synthetic HBGA-VLPs blocking assay showed that the blocking rate in cGAMP+ VLPs immunization group were significantly higher than that in Al(OH)3+ VLPs immunization group when using the same dosage of VLPs. No significant difference in blocking rate was observed between cGAMP+ VLPs (1 μg) and Al(OH)3+ VLPs (10 μg) immunization groups. Conclusion cGAMP significantly enhanced the specific humoral immune response induced by norovirus (GⅡ.4) VLPs in mice as compared with Al(OH)3 adjuvant. It might be used as a novel adjuvant to replace the traditional aluminum adjuvant in the development of norovirus vaccine. Key words: cGAMP; Norovirus; Virus like particles (VLPs); Aluminum adjuvant