Lyme disease is a tick-borne disease caused by the spirochaete Borrelia burgdorferi, which is transmitted enzootically between ticks and their hosts, resulting in approximately 300,000 cases annually in the United States 1,2. Globally, several species within the B. burgdorferi sensu lato complex have been identified as human pathogens, however, in the United States, nearly all Lyme disease is caused by B. burgdorferi sensu stricto (referred to as B. burgdorferi in this Review). Erythema migrans, the characteristic expanding rash, is an indicator of early acute infection, although the disease can also present with a variety of non-specific clinical signs. Spirochaetes enter the human skin at the tick bite site and then use internal periplasmic flagella to migrate to distal tissues, including the heart and joints 3. Untreated infections can progress to multisystemic manifestations including rheumatologic, neurologic and cardiac disease. Similar versions of Lyme disease occur throughout the Northern Hemisphere, where Ixodes tick species are present. In Europe, Lyme borreliosis is caused by B. burgdorferi sensu lato complex spirochaetes (Box 1), which may infect as many as 85,000 persons annually, while in Asia fewer epidemiological studies have been reported, and it is likely that the true incidence is not well understood. The genome of B. burgdorferi consists of an approximately 1-Mb linear chromosome and at least 17 circular and linear plasmids, many of which are highly stable and contain genes that are crucial for survival 4,5 (Box 2). Gene expression is highly regulated to enable the spirochaete to adapt to the different environments as it cycles between an arthropod host and a vertebrate host 6. External cues from the host, such as temperature, pH, CO 2 levels and other biotic factors, as well as host species are important factors that regulate gene expression in B. burgdorferi 7-10. B. burgdorferi undergoes several changes during transmission from the tick to the host to adapt to the new conditions. At the bite site, the spirochaete must evade the immune defences of the mammalian host to extravasate and establish infection in other tissues. Although B. burgdorferi genome encodes several proteins to facilitate these functions, it also relies heavily on interactions with tick salivary proteins injected into the bite site during the initial stage of vertebrate infection. Understanding how the spirochaetes and the tick host interact is crucial to better understand infection, pathogen transmission and potential targeted therapies. In the United States, most tick-borne infections are transmitted by the bite of the blacklegged tick, Ixodes scapularis, including infections with B. burgdorferi, Borrelia miyamotoi, Borrelia mayonii, Babesia microti, Ehrlichia muris eauclairensis, Anaplasma phagocytophilum and Powassan virus. This three-host tick species is the primary vector for Lyme disease-causing B. burgdorferi spirochaetes. The life cycle of I. scapularis spans 2-4 years and includes egg, larval, nymphal and adult s...

This report demonstrates that oncolytic measles virotherapy in combination with aPD-1 blockade significantly improves survival outcome in a syngeneic GBM model and supports the potential of clinical/translational strategies combining MV with αPD-1 therapy in GBM treatment.

These findings document a key mechanism of tumor resistance to oncolytic MV therapy and describe for the first time the development of a prediction algorithm to preselect for oncolytic treatment or combinatorial strategies.

An Ixodes scapularis saliva mRNA vaccine induces tick resistance and prevents Borrelia burgdorferi infection in guinea pigs.