Characterization of a live-attenuated retroviral vaccine demonstrates protection via immune mechanisms
U Dittmer1, D M Brooks, K J Hasenkrug
1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. udittmer@atlas.niaid.nih.gov
Abstract:
Live-attenuated retroviruses have been shown to be effective retroviral vaccines, but currently little is known regarding the mechanisms of protection. In the present studies, we used Friend virus as a model to analyze characteristics of a live-attenuated vaccine in protection against virus-induced disease. Highly susceptible mice were immunized with nonpathogenic Friend murine leukemia helper virus (F-MuLV), which replicates poorly in adult mice. Further attenuation of the vaccine virus was achieved by crossing the Fv-1 genetic resistance barrier. The minimum dose of vaccine virus required to protect 100% of the mice against challenge with pathogenic Friend virus complex was determined to be 10(3) focus-forming units of attenuated virus. Live vaccine virus was necessary for induction of immunity, since inactivated F-MuLV did not induce protection. To determine whether immune cells mediated protection, spleen cells from vaccinated donor mice were adoptively transferred into syngeneic recipients. The results indicated that immune mechanisms rather than viral interference mediated protection.
Insights
Live-attenuated retroviral vaccines, like Friend murine leukemia helper virus (F-MuLV), require live virus for protection against disease. Immune cells, not viral interference, mediate this protection.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Live-attenuated retroviruses show promise as vaccines, but their protective mechanisms remain unclear.
- Friend virus serves as a model to investigate retroviral vaccine efficacy and protection mechanisms.
Purpose of the Study:
- To analyze the characteristics of a live-attenuated vaccine against Friend virus-induced disease.
- To determine the dose of attenuated F-MuLV required for complete protection.
- To elucidate whether immune cells or viral interference mediate protection.
Main Methods:
- Mice were immunized with a live-attenuated nonpathogenic Friend murine leukemia helper virus (F-MuLV), further attenuated by crossing the Fv-1 genetic barrier.
- The minimum protective dose of the attenuated F-MuLV was determined.
- Immunity was assessed by comparing protection from live versus inactivated F-MuLV.
- Adoptive transfer of spleen cells from vaccinated mice into recipients was performed to evaluate immune cell-mediated protection.
Main Results:
- A dose of 10(3) focus-forming units of attenuated F-MuLV was the minimum required to protect 100% of mice against pathogenic Friend virus complex challenge.
- Live vaccine virus was essential for inducing protection; inactivated F-MuLV did not confer immunity.
- Adoptive transfer of spleen cells from vaccinated mice into naive recipients conferred protection, indicating immune cell involvement.
Conclusions:
- Live-attenuated retroviral vaccines, exemplified by F-MuLV, necessitate live virus for effective immunity.
- Immune mechanisms, mediated by immune cells, are responsible for protection conferred by this live-attenuated retroviral vaccine, rather than simple viral interference.
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