Abstract
An excellent example of a novel vaccine approach is presented by Hofstetter and colleagues. Using a mouse model, the authors have developed a peptide vaccine against polyomavirus that elicits protective CD8 T cells that are restricted by oligomorphic or nonpolymorphic major histocompatibility complex (MHC) class Ib molecules. Consequently, the T cell responses elicited by this approach are highly cross-reactive and support the concept that immunization with a single MHC class Ib-restricted peptide can expand CD8 T cells in MHC class Ia allogeneic hosts. Another novel vaccine approach is presented by Machain-Williams and colleagues. It was known that immune response to mosquito-transmitted West Nile virus (WNV) was biased to a Th2-type immune response in flavivirus-susceptible mice, but not flavivirus-resistant mice, due to factors present in arthropod salivary proteins. The authors hypothesized that immunization with mosquito salivary gland extracts with a Th1-biasing adjuvant would prevent Th2 polarization following a mosquito bite and enhance resistance to WNV. Indeed, their data indicate that this strategy enhanced Th1 responses and significantly reduced susceptibility to WNV infection. The development of a mosquito salivary protein vaccine might be a novel strategy to control arthropod-borne viral pathogens such as WNV.
Enhancing the CD8 response is also thought to be important for improving the efficacy of some existing vaccines. Manickam and colleagues have considered this option for vaccines against porcine respiratory and reproductive syndrome virus (PRRSV), an economically important disease of pigs worldwide. Since currently used PRRSV vaccines provide incomplete protection, the authors investigated whether whole cell lysates of Mycobacterium tuberculosis could serve as a mucosal adjuvant to modified live PRRSV vaccine in pigs in previous work and further investigated lung pathology in their current report. The data indicate that the adjuvants induced a favorable anti-PRRSV immune microenvironment in the lungs and facilitated viral clearance. These data may have implications for other veterinary vaccines. However, a cautionary note is presented by Diaz et al. who show that a DNA-based PRRSV exhibited exacerbated clinical signs following subsequent viral challenge.
The appropriate choice of antigen in a subunit vaccine is presumably one of the keys to the success of a vaccine. In this regard, Bao and associates have developed a DNA vaccine based on Chikungunya virus (CHIKV) envelope and nonstructural genes. Their data indicate that the combination of the nonstructural gene with the envelope gene substantially enhanced vaccine efficacy (as compared to a vaccine with envelope alone) suggesting some kind of adjuvant effect. Du and co-workers also address the adjuvant issues with DNA vaccines. In this case, the authors tested the capacity of LIGHT, a member of the TNF superfamily, to serve as an adjuvant for a DNA vaccine against human immunodeficiency virus. The data showed that antibody and T cell responses were enhanced when the LIGHT gene was included in the vaccine construct. The hope is that this approach will be effective in other vaccine constructs. The form of the protein expressed in a vaccine is also important, an issue that has been addressed by Noisumdaeng and colleagues. These authors have developed a recombinant vaccinia virus harboring the full length hemagglutinin (HA) gene from a highly pathogenic avian influenza and assessed the immunogenicity of the expressed HA protein using goat antiserum, mouse monoclonal antibodies, and human sera. They note that the HA protein was immunogenic in mice, but that lot-to-lot variation of the recombinant HA produced in the baculovirus-insect cell system that might prove to be problematic.
One of the difficulties in making vaccines to some viruses is their ability to modulate, or evade, the immune response that is directed against them. Three articles in the current issue of Viral Immunology directly address this issue. Park and colleagues have investigated the capacity of Coxsackievirus B3 (CVB3) to regulate MHC class II-mediated presentation of viral antigens as a mechanism of immune escape. Their data suggest that the IK cytokine plays a role in downregulating MHC class II expression on B cells during CVB3 infection through the induction of cAMP. In another example of viral immune modulation, Zhao and Tyrrell studied the ability of myeloid dendritic cells (mDC) to kill T cells during a chronic hepatitis C virus (HCV) infection. Interestingly, chronically HCV-infected patients' T cells expressed increased levels of PD-1 compared to healthy T cells, suggesting that mDCs may eliminate protective T cells during chronic HCV infection. These data highlight a novel mechanism of HCV immune evasion. In another example of immune modulation, recent data suggest that co-infection with HIV type 1 (HIV-1) and human T lymphotropic virus type 2 (HTLV-2) delays progression to AIDS when compared to isolated HIV-1 infection. Balistrieri and associates link this effect to the capacity of the HTLV-2 transcriptional activating gene, Tax2, to induce CC-chemokines, which play a major role in innate immune responses to HIV-1. The data suggest that HTLV-2 alters innate immune responses in macrophagic reservoirs of HIV-1 in HIV-1/HTLV-2 co-infected individuals. Importantly, these findings have implications for the development of HIV-1 treatments.
The remaining three articles in this issue of Viral Immunology address clinical problems. Oumerzouk and co-workers present a case study of neuromyositis associated with cytomegalovirus (CMV) infection in an immunocompetent patient and note that an awareness of the association between CMV infection and vasculitis may have important therapeutic consequences. Kchouk and others have analyzed HCV strains from Tunisian hemodialysis patients and identified the number and types of strains present, including a suspected new subtype of HCV4. And finally, Singh and colleagues address mechanisms regulating IL-17 expression in HIV-1 infected Indian individuals, suggesting a key role for several transcription factors.
Taken together, the current issue of Viral Immunology offers exciting new insights into the development of the next generation of vaccines. Additional papers complement the topic by introducing novel concepts in viral immune evasion and offering some clinical perspectives to viral infections. I would like to thank all of the authors for their excellent contributions to the field.