|Kehrli Jr, Marcus|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 8/15/2007
Publication Date: 11/8/2007
Citation: Kehrli, Jr., M.E., Vincent, A.L., Richt, J.A., Wesley, R.D., Lager, K.M., Ridpath, J.F., Kimura, K., Roth, J.A. 2007. Virus vaccine research at the National Animal Disease Center: lessons from swine influenza virus and bovine viral diarrhea virus [abstract]. The Changing Landscape of Vaccine Development: Vaccines for Global Health. The University of Texas Medical Branch, Sealy Center for Vaccine Development. p. 14 Interpretive Summary:
Technical Abstract: The continuing emergence of novel subtypes and genetic variants of swine influenza viruses (SIV) causing swine flu challenges our ability to effectively manage this high morbidity disease among swine. New strategic approaches for vaccine development must be considered to keep up with the ever-evolving SIV as well as to overcome the hurdle of maternal antibody interference with detectable humoral responses to inactivated and modified live virus (MLV) vaccines. The role of specific gene segments reassorted in emerging SIV isolates has emerged as critical in altering influenza strain virulence. Particular reassortants may also be a consequence of immunological pressure on SIV within a herd. Therefore, development of vaccines with heterologous and/or heterosubtypic protection has become a significant need for the swine industry. To effectively manage SIV vaccine development will require collaboration with diagnostic laboratories and veterinary practitioners to maintain a repository of relevant field isolates; establishing an improved understanding of the correlation between in vitro cross-reactivity and in vivo cross-protection; the use of reverse genetics to develop safe attenuated MLV; the use of adenovirus vectored vaccines to overcome/bypass maternal antibody interference and a better understanding of the appropriate timing for vaccination. The efficacy of the cold-adapted MLV vaccine in human medicine has paved the way for investigating MLV-based vaccines in swine medicine. Moreover, research on unrelated livestock diseases has demonstrated neonatal vaccination with a MLV or vectored vaccine in livestock can successfully protect animals when administered in the face of high levels of interfering maternal antibodies. This result may be achieved through the use of vectored vaccines or through MLV induction of pathogen specific T lymphocytes in newborn animals. Paradoxically, after maternal antibodies disappear in neonates primed with a MLV or vectored vaccine, an anamnestic humoral immune response occurs following live pathogen challenge or boost with an inactivated vaccine, even in the absence of a detectable primary humoral response. The demonstrated ability to overcome/bypass maternal antibody indicates we can vaccinate newborns to prevent a period of vulnerability to disease that exists as maternal immunity declines but before vaccination has been traditionally used after weaning. In addition to the improved protection seen with MLV vaccines, it has been shown that strain, route of administration, and use of vaccine additives can play a role in enhancing heterologous or heterosubtypic protection. Swine influenza research at the NADC is addressing each of these areas. In addition, to more fully understand experimental vaccine efficacy, the cell-mediated and humoral immune responses at the systemic and mucosal levels are being evaluated in our animal studies.