DNA vaccine prime followed by boost with live attenuated virus significantly improves antigen-specific T cell responses against human cytomegalovirus.
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-γ. 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.
Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA; Department of Pathology; University of Massachusetts Medical School; Worcester, MA USA.
Anna
A
Gil
Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
Siyuan
S
Shen
Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
Scott
S
Coley
Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA; Department of Pediatrics; University of Massachusetts Medical School; Worcester, MA USA.
Laura
L
Gibson
Division of Translational Vaccine Research; Beckman Research Institute of the City of Hope; Duarte, CA USA.
Don J
DJ
Diamond
Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
Shixia
S
Wang
Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
Shan
S
Lu
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D007371:Interferon-gamma
DNA vaccine; IE-1; gB; human cytomegalovirus; pp150; pp65; prime–boost