Summary auto-generated
This study investigated whether naked DNA encoding measles virus haemagglutinin (HA) could induce class I-restricted cytotoxic T lymphocytes (CTLs) when administered via mucosal routes in mice. Researchers tested four mucosal immunization routes: nasal, oral (intragastric), intrajejunal, and buccal. A single nasal immunization with the DNA plasmid induced HA-specific CTL responses in spleen cells, though booster doses did not enhance the response. Oral and intrajejunal routes produced weaker CTL responses, but these could be significantly potentiated by co-administering cholera toxin or cationic lipids (DOTAP). Buccal mucosa immunization also induced CTL responses. The CTL activity was confirmed to be class I-restricted by testing against mismatched target cells. These findings demonstrate that mucosal DNA vaccination with naked plasmids can effectively generate specific CTL responses against measles virus, offering a potentially improved approach over live attenuated vaccines for global immunization campaigns.
Key findings
- Single nasal immunization with DNA plasmid encoding measles HA induced significant HA-specific CTL responses (30% specific lysis at 30:1 effector-to-target ratio)
- Oral and intrajejunal routes produced weaker CTL responses that were significantly enhanced by cholera toxin or DOTAP adjuvants
- Buccal mucosa immunization successfully induced CTL responses, likely due to dendritic cells present in the buccal epithelium
- Booster immunization via the nasal route did not increase CTL activity compared to single-dose immunization
- Mucosal DNA vaccination demonstrates potential as an alternative to live vaccines for measles immunization, particularly in immunocompromised populations
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Abstract
We have investigated the class I-restricted CTL response specific for measles virus haemagglutinin (HA) in the spleens of mice immunized by various mucosal routes with a DNA plasmid carrying the HA gene (pV1j- HA). A single immunization with recombinant DNA injected in the buccal mucosa induced an HA-specific CTL response. Similarly, nasal immunization with the DNA vaccine induced primary CTLs against measles virus HA. Booster immunization did not enhance the CTL activity. Oral or intrajejunal immunization with the plasmid induced a CTL response of lower magnitude. However, this could be potentiated by co- administration of the mucosal adjuvant cholera toxin or cationic lipids (DOTAP). These data show that a CTL response can be generated by mucosal vaccination using DNA vaccines.