Novel Protein and Poxvirus-Based Vaccine Combinations for Simultaneous Induction of Humoral and Cell-Mediated Immunity

Abstract

The presence of both cell-mediated and humoral immunity is important in protection from and clearance of a number of infectious pathogens. We describe novel vaccine regimens using combinations of plasmid DNA, poxvirus and protein to induce strong Ag-specific T cell and Ab responses simultaneously in a murine model. Intramuscular (i.m.) immunization with plasmid DNA encoding the middle Ag of hepatitis B (DNA) concurrently with a commercial hepatitis B virus (HBV) vaccine (Engerix-B) followed by boosting immunizations with both modified vaccinia virus Ankara (MVA) encoding the middle Ag of HBV and Engerix-B induced high levels of CD4+ and CD8+ T cells and high titer Ab responses to hepatitis B surface Ag (HbsAg). Substitution of Engerix-B with adjuvant-free rHBsAg induced similar T cell responses and greatly enhanced Ab levels. Repeated immunizations with recombinant or nonrecombinant MVA mixed with Ag induced higher titers of Abs compared with immunization with either Ag or Engerix-B further demonstrating this novel adjuvant effect of MVA. The poxviruses NYVAC, fowlpox (FP9) and ALVAC, and to a lesser extent, adenovirus, also displayed similar adjuvant properties when used in combination with rHBsAg. The use of poxviruses as an adjuvant for protein to concurrently induce Ag-specific T cells and Abs could be applied to the development of vaccines for many diseases, including HIV and malaria, where both cell mediated and humoral immunity may be important for protection.

Improved adjuvanting of seasonal influenza vaccines: Preclinical studies of MVA‐NP+M1 coadministration with inactivated influenza vaccine

“…An influenza vaccination platform capable of generating both cellular and humoral responses has the potential to improve vaccine efficacy and provide protection in pandemic situations. The use of poxviruses as an adjuvant for protein has previously been reported in a hepatitis B mouse model [21]. We assessed a similar strategy in the context of influenza vaccines.…”

Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic

“…At the moment, the reason for this observation is unclear and may be related to variables such as T cell-independent Ab responses to repetitive viral antigens, stimulatory effects of innate immune responses triggered by the vaccine vector, or delayed expression of HIV immunogens upon vaccination. Interestingly, a recent report has demonstrated that poxvirus-based vaccines are themselves adjuvants for coadministered proteins (29). Therefore, aerosol vaccination with NYVAC or MVA in conjunction with a protein subunit vaccine may induce genital immunogen-specific IgA responses as well as further boosting systemic humoral responses.…”

Targeting of Antigen to Dendritic Cells with Poly(γ-Glutamic Acid) Nanoparticles Induces Antigen-Specific Humoral and Cellular Immunity

“…Novel vaccine candidates being developed are capable of inducing both cellular and humoral immune responses (1,2). For instance, vaccines against intracellular pathogens such as HIV type 1 and malaria are required to induce strong cellular immune responses, whereas vaccines targeting extracellular microorganisms have to induce humoral immune responses (3)(4)(5)(6)(7).…”