Vaccine Development

It is well established that the introduction of vaccination regimens has significantly reduced the burden of infectious diseases in the world today. Furthermore, smallpox and Rinderpest viruses have been completely eradicated from the environment and polio virus is on the cusp of eradication. Despite these advances, we still lack effective vaccines to many significant human pathogens and several of our currently used vaccines could be further improved. Therefore, this issue of Viral Immunology is focused on vaccine improvement and enhancement. One example of a vaccine that remains problematic is the herpes simplex virus 2 (HSV-2) vaccine. Most HSV-2 vaccines tested in humans to date contain just one or two immunogens and presumably lack the antigenic breadth that is necessary to elicit effective cellular immunity. In this context, Bagley and colleagues test the hypothesis that a polyvalent DNA vaccine expressing a combination of HSV-2 antigens in the context of a T helper 1 polarizing adjuvant would exhibit enhanced efficacy in eliciting cellular immune responses. The authors show that their interleukin-12 adjuvanted multivalent DNA vaccine generated substantially greater protection against a high-dose HSV-2 vaginal challenge than a subunit vaccine adjuvanted with alum and monophosphoryl lipid A in a mouse model. Although this is an advance in vaccine efficacy, the authors are aware that further improvements in the vaccine will be needed.

Another vaccine that has proved difficult to develop is the vaccine against hepatitis C virus (HCV). Kitagawa and colleagues point out that they had previously generated an oral HCV vaccine by using Bifidobacterium displaying the HCV-nonstructural protein 3 (NS3) polypeptide. To further improve this vaccine, the authors included interferon-α as an adjuvant in the vaccine formulation and showed that this combination induced strong cellular immunity against the NS3 protein in a mouse model.

Several other articles in this issue of Viral Immunology address other aspects of vaccine efficacy. A vaccine that has been in use for several decades is the Marek's disease vaccine. This vaccine protects against the causative agent Marek's disease virus in domestic chickens, but the underlying mechanisms of vaccine-induced protection are unclear. Heidari and colleagues discuss the various mechanisms that might be at play. Another vaccine that is in common use is the rabies vaccine. Asgary and colleagues have developed an antibody-binding test for determining the potency of different rabies vaccine formulations. The authors' findings suggest that their test would be excellent for determining rabies vaccine potency during in-process quality control tests. Finally, Hosseini and colleagues have designed a multi-epitope universal vaccine that is specific for major human papilloma virus structural proteins by using bioinformatic approaches.

Other articles in this issue of Viral Immunology focus on different aspects of immune regulation against viral infections. Terzieva and colleagues show that interferon-γ (IFN-γ) impacts the proliferative capacity of immune T cells by influencing the regulatory (Treg) population. They suggest that Tregs may effectively control lymphocyte proliferation, but may be less effective at suppressing antigen-specific IFN-γ production from effector T lymphocytes. Huang and colleagues have investigated the expression of programmed death ligand-1 (PDL-1) expression on circulating monocytes and B cells in hepatitis B virus (HBV)–infected patients at chronic and advanced stages of infection. The authors find that PDL-1 expression on CD14+ monocytes and CD19+ B cells correlated with clinical parameters of disease and could be utilized as a clinical indicator of disease progression. In another study related to HBV infection, Cheng and colleagues show that the HBV surface antigen promotes the invasion of HBV-related hepatocellular carcinoma cells via upregulation of Toll-like receptor 2 (TLR2). The authors suggest that the interaction between TLR2 and HBV surface antigen may contribute to the poor prognosis of HBV-related hepatocellular carcinoma. Keib and colleagues point out that infection with adenovirus is a major cause of infectious mortality in children after hematopoietic stem cell transplantation. Adoptive transfer of adenovirus-specific T cells is a possible therapeutic approach, but few suitable adenoviral peptide epitopes have been described. In this regard, the authors report the identification of an adenovirus T cell epitope that may be particularly useful for adoptive T cell transfer therapy of adenovirus infection. Finally, Trang and colleagues hypothesize that fetal monocytes and monocyte-derived macrophages might express high levels of antiviral factors on transmission of HIV in utero. However, their data are not consistent with the hypothesis that increased expression of antiviral genes in fetal myeloid cells confers immune protection to fetuses in utero. These data further extend the body of data on the immune protection of fetuses.

Finally, Graves' disease is an autoimmune disease that causes hyperthyroidism and is often linked to the reactivation of Epstein Barr Virus (EBV)-infected B lymphocytes. Nagataa and colleagues have analyzed EBV-infected B cells and show that immunoglobulin production is catalyzed by activation-induced cytidine deaminase which is regulated by EBV latent membrane protein-1 and nuclear factor-κB. The authors suggest that this mechanism results in the rescue of autoreactive B cells that potentially contribute to the development and exacerbation of autoimmune diseases, such as Graves' disease.

I thank all the authors for their excellent contributions to the journal and all the reviewers for their efforts to oversee the quality of articles accepted for publication.