The field of vaccine development is getting a boost from new research that has identified a promising vaccine delivery approach, which in animal studies produced long-term immune protection after just one immunization.
University of Pittsburgh researchers, who report their findings in the journal Immunity, say the method has particular relevance for efforts aimed at preventing or controlling infectious diseases, such as HIV or influenza, or stopping the growth of cancer. In one set of studies using this delivery approach, a single immunization halted the progression of melanoma and significantly extended survival in a mouse model.
The approach makes use of an inactivated retrovirus, in this case, a modified lentiviral vector more commonly known for its ability to carry functional genes in certain types of gene therapy. Viral vectors in general have been of practical interest to vaccine researchers for their potential to deliver antigens from disease-causing microbes, or even cancer, in order to efficiently build immune defenses against such intruders. To date, the lentivirus has been overlooked in vaccine research. But, according to Pitt investigators, it has distinct advantages that make it a more promising approach for vaccine development than other viral vector or DNA-based vaccine approaches previously studied.
According to results of their studies, a single injection of the lentivector containing either a hepatitis B virus antigen, a melanoma tumor antigen, or a commonly studied model antigen induced a more potent and notably, long-lasting immune response compared to other immunization approaches. A population of specialized immune cells that reside within the top layers of the skin is due much of the credit, say the authors.
"Skin dendritic cells have long been considered the immune system's first line of defense," explains Louis D. Falo, Jr., M.D., Ph.D., professor and chairman of the department of dermatology, University of Pittsburgh School of Medicine, and the study's senior author. "But recent studies that looked at different viral vectors, including the most commonly studied vaccinia vector, have challenged this notion, suggesting that skin dendritic cells are not as important as the classical paradigm maintained. We find that with the lentivirus, it's precisely these skin dendritic cells that are responsible for the vector's more potent immune induction and sustained protection."