Vaccines Against Human and Animal Viruses

The current issue of Viral Immunology includes several articles that focus on the development of vaccines to a number of different viruses. Respiratory syncytial virus (RSV) infection can induce severe respiratory symptoms and poses a serious health problem in young children, immunocompromised patients, and the elderly. Burbulla et al. point out that the development of an effective vaccine is an urgent priority. To address this issue, the authors have focused on human leukocyte antigen (HLA)-restricted epitopes from RSV and identified one new HLA-A*02-restricted and two new HLA-A*01-restricted peptide epitopes from the viral polymerase. Flow cytometric analysis of blood from healthy donors identified T cells specific for these epitopes that were functional in terms of gamma-interferon production. The authors speculate that these peptide antigens could be included in a peptide-based RSV vaccine designed to stimulate defined CD8 T-cell responses.

Human enterovirus 71 (EV-A71) causes hand-foot-and-mouth disease and has become an important public health issue in recent years. Currently, an effective vaccine is not available. The majority of EV-A71 vaccine candidates have been developed for parenteral immunization, but these vaccines tend to induce poor mucosal responses. Zhang and colleagues speculate that oral vaccines may be a better alternative since they induce effective mucosal and systemic immunity and are easy to administer. In this context, the authors have generated a vaccine in which the major immunogenic capsid protein of EV-A71 is displayed on the surface of Saccharomyces cerevisiae. Oral administration of the vaccine to mice induced systemic humoral and mucosal immune responses, including virus-neutralizing titers, VP1-specific antibody, and the induction of Th1 immune responses. In addition, immunization of mother mice conferred protection in neonatal mice against the lethal EV-A71 infection. This vaccine is showing considerable promise for human vaccination.

Another significant human pathogen is human papillomavirus (HPV), which is associated with the development of cervical cancer. Although current prophylactic vaccines prevent infection, they do not help to eliminate existing infections or lesions. In this regard, Toledo et al. have developed an HPV vaccine that combines both prophylactic and therapeutic properties. The vaccine comprises chimeric capsomers designed to elicit antitumor cellular responses, while conserving antibody neutralizing epitopes. The authors show that the bacterially produced chimeric vaccine elicited an immune response that inhibited the growth of tumors in a mouse model. The data suggest that the chimeric protein may be an effective therapeutic vaccine that could help in eliminating HPV16-positive low-grade cervical lesions as well as persistent viral infections.

The fourth virus addressed in this issue of Viral Immunology is avian influenza virus (AIV). The virus is a mucosal pathogen that gains entry into host chickens through respiratory and gastrointestinal routes. Recent advances in vaccine development have included the use of nanoparticle emulsion delivery systems, such as poly (d,l-lactic-co-glycolic acid) (PLGA) nanoparticles, to enhance antigen-specific immune responses. Singh and colleagues note that the Toll-like receptor 21 ligand, CpG oligodeoxynucleotides, is immunostimulatory in chickens and have analyzed its adjuvant potential when encapsulated in PLGA. Their data indicate that encapsulated CpG oligodeoxynucleotides AIV vaccines administered by the aerosol route elicited higher mucosal responses than nonencapsulated CpG oligodeoxynucleotides. The findings may have broader implications for vaccine design and delivery.

The last vaccine article in this issue focuses on noroviruses (NoV), which account for the majority of diagnosed cases of viral acute gastroenteritis worldwide. Tamminen et al. point out that serum antibodies that block the binding of NoV to their putative receptor correlate with protection. However, the role of mucosal antibodies in protection is largely unknown. The authors immunized mice either intramuscularly or intranasally with an NoV vaccine and show that although both immunization routes induced similar blocking activity in serum, only the intranasal route generated blocking antibodies in mucosa. The results indicate that only the mucosal immunization route induces the development of functional anti-NoV IgA at mucosal surfaces.

Finally, other articles in this issue of Viral Immunology address the innate immune response to viral infections. Jinushi and colleagues have examined the changes in interferon-stimulated gene (ISG) expression in cells infected with different strains of measles virus (MeV). The wild strain of genotype D3 was the most potent inhibitor of MeV infection-induced ISG expression and produced the highest titer of infectious viral particles. In contrast, the laboratory strain Edmonston triggered the highest levels of MeV infection-induced ISG expression and produced the lowest titer of infectious particles, indicating a possible limitation for studies with the laboratory strain. And in another article, Gambarino and colleagues have evaluated mir-146a expression in kidney transplant patients during human cytomegalovirus infection. In contrast to other studies, the expression levels of mir-146a were similar in individuals with high viral load, low viral load, or no viral load. These data suggest that more needs to be done to understand the relationship between mir-146a and human cytomegalovirus infection.

I would like to thank all of the authors for their fine research contributions to the journal and all of the reviewers for their help in maintaining the high quality of articles published.