Mucosal vaccine vectors: replication-competent versus replication-deficient poxviruses.

The mucosal surfaces of the respiratory, gastrointestinal, and genitourinary tract are entry points for a variety of pathogens and they serve as the first line of defense against infection. To prevent transmission of mucosal pathogens, it is often necessary to target the vaccine to the mucosal surface. Viral vectors, such as poxviruses expressing gene inserts, capable of overcoming the formidable array of host defenses at the mucosal surfaces, are an attractive vaccination strategy for mucosal immunization against infectious diseases. Replication-competent vectors, such as vaccinia, are highly effective, but have a number of safety concerns that may limit their widespread use in humans. In contrast, replication-deficient vectors, such as modified vaccinia ankara (MVA), ALVAC, and NYVAC, may be safer vectors than live vectors, but these vectors may not be as effective at inducing immune responses. Co-delivery of viral vectors with genetic adjuvants (cytokines) or deletion of certain immunomodulatory genomic sequences from these viral vectors may increase vaccine efficiency and are promising strategies for a new generation of mucosal vaccines.

Virus-like particles: designing an effective AIDS vaccine.

Viruses that infect eukaryotic organisms have the unique characteristic of self-assembling into particles. The mammalian immune system is highly attuned to recognizing and attacking these viral particles following infection. The use of particle-based immunogens, often delivered as live-attenuated viruses, has been an effective vaccination strategy for a variety of viruses. The development of an effective vaccine against the human immunodeficiency virus (HIV) has proven to be a challenge, since HIV infects cells of the immune system causing severe immunodeficiency resulting in the syndrome known as AIDS. In addition, the ability of the virus to adapt to immune pressure and reside in an integrated form in host cells presents hurdles for vaccinologists to overcome. A particle-based vaccine strategy has promise for eliciting high titer, long-lived, immune responses to a diverse number of viral epitopes against different HIV antigens. Live-attenuated viruses are effective at generating both cellular and humoral immune responses. However, while these vaccines stimulate immunity, challenged animals rarely clear the viral infection and the degree of attenuation directly correlates with protection from disease. Further, a live-attenuated vaccine has the potential to revert to a pathogenic form. Alternatively, virus-like particles (VLPs) mimic the viral particle without causing an immunodeficiency disease. VLPs are self-assembling, non-replicating, non-pathogenic particles that are similar in size and conformation to intact virions. A variety of VLPs for lentiviruses are currently in preclinical and clinical trials. This review focuses on our current status of VLP-based AIDS vaccines, regarding issues of purification and immune design for animal and clinical trials.