DNA vaccine prime followed by boost with live attenuated virus significantly improves antigen-specific T cell responses against human cytomegalovirus
Department of Medicine, Division of Infectious Diseases and Immunology; Department of Pathology; Department of Pediatrics
Animals; Antibodies, Viral; Cytomegalovirus; Cytomegalovirus Vaccines; Female; Interferon-gamma; Mice; Mice, Inbred BALB C; T-Lymphocytes; Vaccines, Attenuated; Vaccines, DNA
Immunology of Infectious Disease | Immunopathology | Immunoprophylaxis and Therapy
As a leading cause of congenital infection and a major threat to immunocompromised individuals, human cytomegalovirus (HCMV) is a major global public health concern. Effective HCMV vaccines would need to induce potent and balanced humoral and cellular immune responses. In this pilot study, immunogenicity studies were conducted in mice to examine HCMV antigen-specific antibody and T cell responses when a heterologous prime-boost immunization strategy was tested. DNA vaccines expressing either targets of protective antibody responses (gB and gM/gN) or well characterized T cell immunogens (pp65, pp150, and IE1) were used as the priming immunization while the live attenuated HCMV vaccine Towne strain was used as the boost, which may act like an inactivated vaccine due to the inability of HCMV to replicate in a mouse host. Our data indicate that while DNA vaccines were effective in priming HCMV-specific antibody responses, the final titers of gB- or gM-specific antibodies were not much different from those elicited by using multiple immunizations of HCMV alone. In contrast, DNA priming significantly enhanced T cell responses against gB, pp65, and IE1 as measured by IFN-gamma. However, HCMV alone was not effective in eliciting strong T cell immune responses when used in a mouse host. Our data indicate that the complexity of antigen composition from a large virus, such as HCMV, may affect the profile of immune responses when viral vaccines are used as a boost.
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Citation: Hum Vaccin Immunother. 2013 Oct;9(10):2120-32. doi: 10.4161/hv.25750. Epub 2013 Jul 25. Link to article on publisher's site
Human vaccines and immunotherapeutics
Gil, Anna; Shen, Siyuan; Coley, Scott; Gibson, Laura; Diamond, Don J.; Wang, Shixia; and Lu, Shan, "DNA vaccine prime followed by boost with live attenuated virus significantly improves antigen-specific T cell responses against human cytomegalovirus" (2013). University of Massachusetts Medical School Faculty Publications. 759.