Identifying the gaps in human and veterinary chlamydia vaccine development

Background: Chlamydia infections in humans and animals pose a significant burden on health systems worldwide. While widespread screening, adequate treatment, and prevention programs are helpful to increase awareness and improve screening rates, infection rates are rising. A vaccine is necessary to slow increasing rates, manage negative consequences, and prevent possible antibiotic resistance. We present the current landscape regarding the innovations for commercial vaccine development in a “one-health” context. Methods: We developed a unique dataset containing data of patent documents intended for human and veterinary use, and clinical trials in order to provide a detailed description of the global chlamydia vaccine developments. Results: Analysis of patents and clinical trials intended for human use presented a vaccine field that is underdeveloped, with no commercial human chlamydia vaccine available, and two potential candidates in a phase 1 clinical trial. Comparing innovations concerning chlamydia vaccine developments for both human and veterinary patents, it was clear that these fields are very different and independent of each other. The field is small, and certain companies and researchers show repeated interest. Partnerships among applicants and those involved in chlamydia vaccine innovation would be an important step to take towards innovating and developing an effective vaccine. Conclusions: We have shown that North America is considered, by patent application, to hold the most potential for a chlamydia vaccine, specifically against the Chlamydia trachomatis strain. A new vaccine is likely to be a subunit vaccine with components of the major outer membrane protein antigen

Susceptibility of Thymocytes for Infection by Chicken Anemia Virus is Related to Pre- and Posthatching Development

To investigate the age-dependent mechanism of susceptibility for chicken anemia virus (CAV) infection, we inoculated embryos and chickens of ages between day 9 of embryonic development and day 28 after hatching with CAV. Chicken embryos inoculated at days 9 and 11 of development showed no CAV-infected cells in the thymus, nor in other lymphoid organs. Many CAV-infected cells were detected in the thymic cortex of all chicken embryos inoculated at days 13 and 16 of development and of all chickens inoculated 1, 3, and 7 days after hatching. All embryos and chickens that contained CAV-infected cells in the thymus also contained CAV-infected cells in the bone marrow, but not in the bursa of Fabricius or the spleen. In chickens inoculated at days 14 and 21, only few CAV-infected cells were detected in the thymus, whereas these cells were not detected in thymi of 28-day-old inoculated chickens. Depletion of the thymic cortex was only detected in chickens inoculated from day 16 of embryonic development till day 21 after hatching. Only hematocrit values of the chickens inoculated 1 and 3 days after hatching were below normal. The rationale for the simultaneous susceptibility of cells of the T-cell lineage and cells of the erythrocyte lineage is discussed. As far as the thymus is concerned, the absence of clinical and microscopical signs of CAV infection in older chickens and the inability of CAV to infect embryos at days 9 and 11 of embryonic development may be caused by a lack of susceptible thymocytes. In view of the three waves of thymic precursor cells that populate the thymus during ontogeny, as described by Le Douarin and colleagues, we hypothesize that CAV only infects thymocytes derived from the second wave of precursor cells

Gene Disruption of Plasmodium falciparum p52 Results in Attenuation of Malaria Liver Stage Development in Cultured Primary Human Hepatocytes

Difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated Plasmodium parasites. Immunizations with sporozoites that are attenuated by radiation (RAS) can induce strong protective immunity both in humans and rodent models of malaria. Recently, in rodent parasites it has been shown that through the deletion of a single gene, sporozoites can also become attenuated in liver stage development and, importantly, immunization with these sporozoites results in immune responses identical to RAS. The promise of vaccination using these genetically attenuated sporozoites (GAS) depends on translating the results in rodent malaria models to human malaria. In this study, we perform the first essential step in this transition by disrupting, p52, in P. falciparum an ortholog of the rodent parasite gene, p36p, which we had previously shown can confer long lasting protective immunity in mice. These P. falciparum P52 deficient sporozoites demonstrate gliding motility, cell traversal and an invasion rate into primary human hepatocytes in vitro that is comparable to wild type sporozoites. However, inside the host hepatocyte development is arrested very soon after invasion. This study reveals, for the first time, that disrupting the equivalent gene in both P. falciparum and rodent malaria Plasmodium species generates parasites that become similarly arrested during liver stage development and these results pave the way for further development of GAS for human use