Abstract
As with other vaccination strategies, adjuvants are required to elicit immune responses from non-live vaccine components. Yet adjuvants can be problematic in the sensitive tissues of the respiratory tract. In the current issue of Viral Immunology, Kobayashi and colleagues have evaluated the effectiveness and safety of chitosan derivatives from natural crab shells as adjuvants for intranasal vaccines. The authors show that administration of ovalbumin protein with chitosan microparticles or cationized chitosan induced strong antigen-specific IgA and IgG responses both in mice and cynomolgus monkeys. Importantly, the administration of chitosan derivatives did not appear to have any detrimental effects, suggesting that these derivatives are safe and effective mucosal adjuvants for intranasal vaccination. These advances in adjuvant development may have a significant impact on future intranasal vaccines.
Three additional papers in this issue address various aspects of vaccine development. Hallengärd and colleagues have investigated the capacity of human immunodeficiency virus type 1 (HIV-1), reverse transcriptase (RT) enzyme to serve as a vaccine antigen. Their strategy was to increase the immunogenicity of the protein by deleting non- or low-immunogenic sequences. The authors show that the truncated RT displayed enhanced in vitro expression and cell-mediated immune responses in mice, and speculate that this optimization strategy could be used to enhance the immunogenicity of other RT-encoding DNA vaccines. Another virus for which a vaccine is not available is the newly emerging severe acute respiratory syndrome virus (SARS). Therefore, Li et al. have investigated the immunogenicity and protective efficacy of recombinant proteins corresponding to different domains of the SARS-corona virus spike protein. The authors show that spike protein vaccines can effectively elicit neutralizing antibodies in mice. A challenge for some vaccines is the presence of pre-existing immunity. Noroviruses (NoVs) are a leading cause of acute nonbacterial gastroenteritis in humans and a major question is whether type-specific pre-existing immunity might impair cognate immune response induced by new viral infections or vaccines. Tamminen et al. have investigated this question and conclude that pre-existing immunity to norovirus GII-4 virus-like particles does not impair de novo immune responses to norovirus GII-12 genotype. This finding is important for the development of future vaccines.
A novel approach to the control of infectious disease is the use of bacteriophages, viruses that infect bacteria, to combat bacterial infections, including those caused by antibiotic-resistant bacterial strains. While this is a promising strategy, there is only limited knowledge regarding the influence of bacteriophages on human cells. In this regard, Kurzepa-Skaradzinska and associates have investigated whether T2 and T4 phages (specific to Escherichia coli) and A3 phage (specific to Staphylococcus aureus) impair the bactericidal activities of human granulocytes and monocytes. Their data indicate that bacteriophage preparations do not influence intracellular killing of bacteria by human phagocytes, irrespective of phage preparation, titer, and whether bacteria engulfed by phagocytic cells are sensitive or insensitive to phage. The study supports previous data indicating safety of therapeutic application of phages.
Finally, one article in this issue addresses innate immune responses to viral infection. In a conventional study of innate immunity, Grgić et al. have investigated cytokine gene expression patterns associated with fowl adenovirus (FAdV) infection. The data show that infected birds had higher mRNA expression of interleukin (IL) 18, IL-10, and IFN-γ and lower mRNA expression of IL-8 in spleen and liver. The data suggest that these cytokines might play an important role in driving the immune responses following FAdV-8 infection.
Taken together, the articles in this issue of Viral Immunology offer several new perspectives that will be important for the development of new vaccines and therapeutics against bacterial and viral diseases.