Reorganization of the actin cytoskeleton, as indicated by our microarray studies and by phalloidin staining of F actin, is essential to the pathogenesis of diverse bacterial infections, and pathogens use many different strategies to provoke changes in the cellular cytoskeleton in order to facilitate invasion of tissues, invasion of host cells, or evasion of phagocytosis (as reviewed in [24, 41, 42] ). A different spirochete, Treponema denticola, produces the protein Msp, which disrupts the actin cytoskeleton in neutrophils and fibro-blasts, preventing phagocytosis of the bacterium and inhibiting the cellular migration required to respond to and repair the damage caused by the pathogen and the host response at the site of infection [43, 44] . These activities are likely to facilitate invasion and colonization of periodontal tissues by T. denticola. Previous work by another laboratory demonstrated that L. interrogans Copenhageni crosses MDCK canine kidney epithelial cell layers in culture more rapidly than does L. biflexa Patoc [45] , but without significant disruption to the cell layers or the actin cytoskeleton. Consistent with these results, in experiments not shown here we also observed no significant damage to NRK (normal rat kidney) 293 (human kidney) or HEp-2 (human laryngeal) epithelial cell layers infected with L. interrogans Canicola or L. interrogans Copenhageni. The calculations of the proportions of bacteria crossing the cell layers differed between the two studies, but our protocol accounted for the replication of the L. interrogans Canicola and Copenhageni in the co-cultures, while the L. biflexa Patoc did not replicate (data not shown). Thus the endothelial cells tested here respond very differently to the bacteria than did the MDCK epithelial cells, and our results are the first to suggest a mechanism: disruption of actin dynamics by bacterial attachment to the cell surface. Thus, while L. interrogans has not been shown to secrete a toxin that modifies actin, the bacteria are able to manipulate the actin cytoskeleton indirectly. Even the pore forming toxin activity reported for Leptospira [46, 47] does not appear to have as large an effect, as the endothelial cells here were viable throughout the experiments. The leptospires may be able to establish disseminated infection in part due to the binding of the bacteria to one or more mammalian cell surface receptors that in turn, regulate the dynamics of the actin cytoskeleton in the mammalian cell. Deciphering the role of, and mechanisms behind, actin rearrangement in response to pathogenic Leptospira will provide insights into the mechanisms that leptospires uses to disseminate to different organs of the host to cause infection and disease, and provides a possible avenue for therapeutic intervention in conjunction with antimicrobial therapy. A Porcine Adenovirus with Low Human Seroprevalence Is a Promising Alternative Vaccine Vector to Human Adenovirus 5 in an H5N1 Virus Disease Model Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration. This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load. Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals. Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5. Experimental adenovirus-based vaccine vectors are promising alternatives to conventional vaccine platforms. In particular, human adenovirus serotype 5 (AdHu5) vectors are well-characterized and are being developed against several infectious disease models including influenza, hepatitis C, dengue and viral hemorrhagic fever viruses [1, 2, 3, 4] . Several candidates have demonstrated unique protective efficacy and can generate robust immune responses in both animal models and clinical trials [4, 5, 6, 7] . Pre-existing immunity against AdHu5 is, however, frequent in the human population and has been associated with undesirable clinical outcomes and the suspension of clinical trials [8, 9, 10] . One promising alternative is the development and evaluation of rare human, chimpanzee, or other mammalian adenovirus vectors with low seroprevalence in humans. A chimeric simian adenovirus 21 vector protected mice against lethal Ebolavirus challenge and generated robust T-cell responses against the glycoprotein in nonhuman primates [11] . A bovine adenovirus 3 (BAV3)-based vaccine previously demonstrated successful protection against avian influenza A virus H5N1 challenge in mice and was able to escape preexisting neutralizing antibodies against AdHu5 [12] . Similarly, a porcine adenovirus 3 (PAV3) vector was successful in several swine vaccination studies against classical swine fever and pseudorabies virus [13, 14, 15] . PAV3-based vaccines were able to evade pre-existing immunity and provide long-term protection in pigs [14] . The antigenic profile and reported in vivo efficacy as an animal vaccine makes the PAV3 vector a promising alternative adenovirus vector for human administration.