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Effects of Rotavirus NSP4 on the Immune Response and Protection of Rotavirus-Norovirus Recombinant Subunit Vaccines
Jingping Hu1, Jinyuan Wu1, Han Cao1
1Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
Insights
Rotavirus nonstructural protein 4 (NSP4) did not enhance mucosal immunity in mice. However, NSP4 showed protective effects against diarrhea when used as a co-immunized antigen.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Diarrheal diseases, particularly rotavirus infections, remain a significant global health threat to young children.
- Parenteral rotavirus vaccines offer a promising alternative to oral vaccines, addressing existing limitations.
- Previous research indicated rotavirus nonstructural protein 4 (NSP4) provided protection against diarrhea via intramuscular injection, but its adjuvant potential on mucosal immunity was unexplored.
Purpose of the Study:
- To investigate the potential adjuvant effects of rotavirus nonstructural protein 4 (NSP4) on mucosal immune pathways.
- To evaluate the efficacy of NSP4 in combination with VP8* antigen in inducing protective immunity against rotavirus via different immunization routes.
Main Methods:
- Mice were immunized via intramuscular and nasal routes with rotavirus antigens, including NSP4 and VP8*.
- Following immunization, mice were challenged with rotavirus Wa or SA11 strains.
- Protective efficacy was assessed by measuring serum IgG antibody titers and IgA levels in bronchoalveolar lavage fluid (BALF), and evaluating protection against diarrhea.
Main Results:
- Nasal immunization resulted in significantly lower serum-specific VP8* IgG antibody titers compared to intramuscular immunization.
- Specific IgA antibodies were largely undetectable in the bronchoalveolar lavage fluid (BALF) of nasally immunized mice.
- NSP4 did not demonstrate an adjuvant effect by increasing specific VP8* antibody titers in either immunization pathway.
Conclusions:
- Rotavirus nonstructural protein 4 (NSP4) failed to elicit adjuvant effects through the mucosal immune pathway in the tested vaccine formulations.
- NSP4, when administered as a co-immunized antigen, stimulated the production of specific binding antibodies that conferred protection against rotavirus-induced diarrhea.
- These findings suggest NSP4's protective role against diarrhea is primarily as an antigen rather than a mucosal adjuvant.
Abstract:
Diarrheal disease continues to be a major cause of global morbidity and mortality among children under 5 years of age. To address the current issues associated with oral attenuated rotavirus vaccines, the study of parenteral rotavirus vaccines has promising prospects. In our previous study, we reported that rotavirus nonstructural protein 4 (NSP4) did not increase the IgG antibody titer of co-immune antigen but did have a protective effect against diarrhea via the intramuscular injection method. Here, we explored whether NSP4 can exert adjuvant effects on mucosal immune pathways. In this study, we immunized mice via muscle and nasal routes, gavaged them with the rotavirus Wa strain or the rotavirus SA11 strain, and then tested the protective effects of immune sera against both viruses. The results revealed that the serum-specific VP8* IgG antibody titers of the mice immunized via the nasal route were much lower than those of the mice immunized by intramuscular injection, and the specific IgA antibodies were almost undetectable in the bronchoalveolar lavage fluid (BALF). NSP4 did not increase the titer of specific VP8* antibodies in either immune pathway. Therefore, in the two vaccines (PP-NSP4-VP8* and PP-VP8*+NSP4) used in this study, NSP4 was unable to perform its potential adjuvant role through the mucosal immune pathway. Instead, NSP4 was used as a co-immunized antigen to stimulate the mice to produce specific binding antibodies that play a protective role against diarrhea.
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