DNA vaccine and dendritic cells (DCs)-based vaccine have emerged as promising strategies for cancer immunotherapy. Fms-like tyrosine kinase 3-ligand (Flt3L) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) have been exploited for the expansion of DC. It was reported previously that combination of plasmid encoding GM-CSF with HER2/neu DNA vaccine induced predominantly CD4þ T-cell-mediated antitumor immune response. In this study, we investigated the modulation of immune responses by murine Flt3L and GM-CSF, which acted as genetic adjuvants in the forms of bicistronic (pFLAG) and monocistronic (pFL and pGM) plasmids for HER2/neu DNA vaccine (pN-neu). Coexpression of Flt3L and GM-CSF significantly enhanced maturation and antigen-presentation abilities of splenic DC. Increased numbers of infiltrating DC at the immunization site, higher interferon-g production, and enhanced cytolytic activities by splenocytes were prominent in mice vaccinated with pN-neu in conjunction with pFLAG. Importantly, a potent CD8 þ T-cell-mediated antitumor immunity against bladder tumors naturally overexpressing HER2/neu was induced in the vaccinated mice. Collectively, our results indicate that murine Flt3L and GM-CSF genes coexpressed by a bicistronic plasmid modulate the class of immune responses and may be superior to those codelivered by two separate monocistronic plasmids as the genetic adjuvants for HER2/neu DNA vaccine.

Cobia, Rachycentron canadum L., is a very important aquatic fish that faces the risk of infection with the bacterial pathogen Photobacterium damselae ssp. piscicida, and there are few protective approaches available that use multiple antigens. In the present study, potent bivalent antigens from P. damselae ssp. piscicida showed more efficient protection than did single antigens used in isolation. In preparations of three antigens that included recombinant heat shock protein 60 (rHSP60), recombinant α-enolase (rENOLASE) and recombinant glyceraldehyde-3-phosphate dehydrogenase (rGAPDH), we analysed the doses that elicited the best immune responses and found that this occurred at a total of 30 μg of antigen per fish. Subsequently, vaccination of fish with rHSP60, rENOLASE and rGAPDH achieved 46.9, 52 and 25% relative per cent survival (RPS), respectively. In addition, bivalent subunit vaccines--combination I (rHSP60 + rENOLASE), combination II (rENOLASE + rGAPDH) and combination III (rHSP60 + rGAPDH)--were administered and the RPS in these groups (65.6, 64.0 and 48.4%, respectively), was higher than that achieved with single-antigen administration. Finally, in combination IV, the trivalent vaccine rHSP60 + rENOLASE + rGAPDH, the RPS was 1.6%. Taken together, our results suggest that combinations of two antigens may achieve a better efficiency than monovalent or trivalent antigens, and this may provide new insights into pathogen prevention strategies.

Background Older adults are at increased risk of pneumococcal disease (PD). V114, an investigational 15-valent Pneumococcal Conjugate Vaccine (PCV), contains all serotypes in 13-valent PCV (PCV13) plus serotypes 22F and 33F. This phase 3 trial evaluated the safety, tolerability and immunogenicity of V114 or PCV13 followed 12 months later by PPSV23 in healthy adults aged ≥50 years. Materials/Method 652 eligible adults were randomised 1:1 to receive V114 or PCV13 followed by PPSV23 12 months later. Solicited and non-solicited adverse events (AEs) were collected after each vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were measured at Day 1, Day 30, Month 12 and Month 13. Results The most common solicited AEs following PCV were injection-site pain, fatigue and myalgia; higher proportions of participants with solicited AEs were observed in the V114 group; however, the differences were not clinically significant, as most AEs were mild and of short duration. The most common solicited AEs following PPSV23 were injection-site pain, injection-site swelling, fatigue and myalgia; these events were comparable across both intervention groups. The proportion of participants with serious AEs were low in both groups and none reported to be vaccine related. No deaths occurred during the study. Serotype-specific OPA geometric mean titres (GMTs) and IgG geometric mean concentrations (GMCs) were comparable between the groups for all 15 serotypes 30 days post-vaccination with PPSV23. OPA GMTs and IgG GMCs were comparable between PCV groups for the 13 shared serotypes and higher in V114 than PCV13 for serotypes 22F and 33F 30 days and 12 months post-vaccination with PCV. V114 elicited an immune response that persisted for at least 12 months. Conclusion Sequential administration of V114 and PPSV23 is well tolerated, immunogenic and generally comparable to PCV13 followed by PPSV23 in healthy adults ≥50 years of age.