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The adjuvant effect of a muramyl dipeptide (MDP) analog on temperature-sensitive Salmonella mutant vaccine
K Onozuka1, H Shinomiya, N Cho
1Department of Microbiology, Jichi Medical School, Japan.
Abstract:
Adjuvant effect of a synthetic muramyl dipeptide analog, MDP-Lys (L18), MurNAc-L-Ala-D-glu[Lys(CO-(CH2)16-CH3)-OH]NH2 on a live Salmonella enteritidis vaccine, a temperature-sensitive mutant Ts-O strain that was obtained from the virulent S. enteritidis No.11 strain and could not grow at 37 degrees C, but could multiply at 25 degrees C as fast as the parent strain, was examined. Although the Ts-O organisms were avirulent and could hardly multiply in vivo when the organisms were injected into C57BL/6 mice and its mutant beige strain, which has a malfunction of phagocytic cells, injection of these mice with Ts-O endowed them with some protective immunity against infection by the virulent No.11 strain. When MDP-Lys(L18) was injected with Ts-O vaccine, the protection and the bactericidal capacity in the peritoneal cavities and spleens of these mice were augmented. MDP-Lys(L18) was still effective when it was injected at 48 h before or after the inoculation of Ts-O vaccine. Its effect was also observed against infection by the virulent S. cholerae-suis Hokkaido strain, a strain that does not share common O-antigenic determinants with the S. enteritidis No.11 or Ts-O strain. In addition, the mice that were inoculated simultaneously with Ts-O organisms and MDP-Lys(L18) were examined 10 days later for their footpad delayed type hypersensitivity reactions against Ts-O antigen. Mice inoculated with MDP-Lys(L18) and Ts-O showed augmented footpad swelling in comparison with the controls. These findings indicate that MDP-Lys(L18) is capable of augmenting the cellular immunity by live vaccine.
Insights
A synthetic muramyl dipeptide analog, MDP-Lys (L18), enhanced the immune response to a live Salmonella enteritidis vaccine. This adjuvant boosted protection and cellular immunity in mice, even when administered separately from the vaccine.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Live bacterial vaccines are crucial for preventing Salmonella infections.
- Adjuvants can enhance vaccine efficacy by stimulating the immune system.
- Muramyl dipeptide analogs are known for their immunomodulatory properties.
Purpose of the Study:
- To evaluate the adjuvant effect of a synthetic muramyl dipeptide analog, MDP-Lys (L18), on a live Salmonella enteritidis vaccine.
- To assess the impact of MDP-Lys (L18) on cellular immunity and protective responses against Salmonella infection.
Main Methods:
- A temperature-sensitive mutant Salmonella enteritidis strain (Ts-O) was used as a live vaccine.
- Mice (C57BL/6 and beige mutant) were vaccinated with Ts-O, with or without MDP-Lys (L18).
- Immune responses were assessed by measuring protection against virulent Salmonella strains, bactericidal capacity, and delayed-type hypersensitivity reactions.
Main Results:
- MDP-Lys (L18) significantly augmented protection and bactericidal capacity when co-administered with the Ts-O vaccine.
- The adjuvant effect was observed even when MDP-Lys (L18) was administered up to 48 hours before or after vaccination.
- Enhanced cellular immunity, indicated by augmented footpad swelling, was observed in mice receiving both Ts-O and MDP-Lys (L18).
Conclusions:
- MDP-Lys (L18) acts as an effective adjuvant, enhancing the cellular immunity induced by a live Salmonella vaccine.
- This synthetic muramyl dipeptide analog shows potential for improving vaccine-induced protection against Salmonella infections.
- The findings suggest MDP-Lys (L18) could be a valuable component in developing more potent Salmonella vaccines.