A vaccine formulated with the major outer membrane protein can protect C3H/HeN, a highly susceptible strain of mice, from a Chlamydia muridarum genital challenge.

C3H/HeN female mice were vaccinated with native Chlamydia muridarum major outer membrane protein (MOMP), using Montanide+CpG or Alum+CpG as adjuvants. Negative control groups were immunized with ovalbumin (OVA) and the same adjuvants. As positive control, mice were inoculated intranasally with live Chlamydia. Mice were challenged in the ovarian bursa with 10(5) C. muridarum inclusion forming units. Six weeks after the genital challenge the animals were caged with male mice and monitored for pregnancy. Mice vaccinated with MOMP+Montanide+CpG developed high levels of C. muridarum-specific antibodies, with a high IgG2a/IgG1 ratio and neutralizing titres. Animals immunized using Alum+CpG had low antibody levels. Cellular immune responses were significantly higher in mice vaccinated with MOMP and Montanide+CpG, but not with Alum+CpG, when compared with negative controls. Following the genital challenge, only 20% (4/20) of mice vaccinated with MOMP+CpG+Montanide had positive vaginal cultures whereas 100% (9/9) of mice immunized with MOMP+CpG+Alum had positive cultures. Of the positive control animals inoculated with live Chlamydia only 15% (3/20) had positive vaginal cultures. In contrast, 100% (20/20) of mice immunized with OVA+CpG+Montanide, or minimal essential medium, had positive cultures. Following mating, 80% (16/20) of mice vaccinated with MOMP+CpG+Montanide, and 85% (17/20) of animals inoculated intranasally with live C. muridarum carried embryos in both uterine horns. No protection against infertility was observed in mice immunized with MOMP and CpG+Alum or OVA. In conclusion, this is the first time that a subunit vaccine has been shown to elicit a protective immune response in the highly susceptible C3H/HeN strain of mice against an upper genital challenge

National Institute of Allergy and Infectious Diseases workshop report: "Chlamydia vaccines: The way forward".

Chlamydia trachomatis (Ct), an intracellular pathogen, is the most common bacterial sexually transmitted infection. In addition to acute cervicitis and urethritis, Ct can lead to serious sequelae of significant public health burden including pelvic inflammatory disease (PID) and infertility. Ct control efforts have not resulted in desired outcomes such as reduced incidence and reinfection, and this highlights the need for the development of an effective Ct vaccine. To this end, NIAID organized a workshop to consider the current status of Ct vaccine research and address critical questions in Ct vaccine design and clinical testing. Topics included the goal(s) of a vaccine and the feasibility of achieving these goals, animal models of infection including mouse and nonhuman primate (NHP) models, and correlates of protection to guide vaccine design. Decades of research have provided both whole cell-based and subunit vaccine candidates for development. At least one is currently in clinical development and efforts now need to be directed toward further development of the most attractive candidates. Overall, the discussions and presentations from the workshop highlighted optimism about the current status of Ct vaccine research and detailed the remaining gaps and questions needed to move vaccines forward

Computational modeling of TC0583 as a putative component of the Chlamydia muridarum V-type ATP synthase complex and assessment of its protective capabilities as a vaccine antigen.

Numerous Chlamydia trachomatis proteins have been identified as potential subunit vaccines, of which the major outer-membrane protein (MOMP) has, so far, proven the most efficacious. Recently, subunit A of the V-type ATP synthase (ATPase; TC0582) complex was shown to elicit partial protection against infection. Computational modeling of a neighboring gene revealed a novel subunit of the V-type ATPase (TC0583). To determine if this newly identified subunit could induce protection and/or enhance the partial protection provided by subunit A alone, challenge studies were performed using a combination of these recombinant proteins. The TC0583 subunit alone and concurrently with TC0582, was used to vaccinate BALB/c mice utilizing CpG-1826 and Montanide ISA 720 VG as adjuvants. Vaccinated animals were challenged intranasally with Chlamydia muridarum and the course of the infection was followed. Mice immunized with individual antigens showed minimal alleviation of body weight reduction; however, mice immunized with TC0583 and TC0582 in combination, displayed weight loss levels close to those observed with MOMP. Importantly, immunization with a combination of recombinant subunit proteins reduced chlamydial inclusion forming units by approximately a log-fold. These protection levels support that, these highly conserved Chlamydia proteins, in combination with other antigens, may serve as potential vaccine candidates

Exposure to strangers does not cause pregnancy distribution or infanticide in the gray-tailed vole

Numerous laboratory studies with at least 12 species of rodents have reported that exposure of females to strange males results in pregnancy disruption or infanticide. The proximate causes and ultimate benefits of these behaviors have been proposed from an evolutionary perspective. To determine if exposure to strange males or females caused pregnancy disruption and (or) infanticide in a resident gray-tailed vole (Microtus canicaudus) population, pregnancy rate and juvenile recruitment were monitored in populations of 12 female and 12 male voles following introduction of unfamiliar adults. These experiments were conducted in 12 0.2 ha enclosures using three treatments and a control. Every 10 days 12 males, six males, or six females were removed and replaced in the three treatments, respectively, or the populations were left unmanipulated in the control (3 replicates/treatment). The time to first parturition, time between parturitions, number of juveniles recruited/parturition, and percent of births followed by lactation did not vary among the controls and three treatments. The only observable effects of treatment were a slight non-significant delay in time to first birth in the 12-male treatment and a slightly significant difference in the number of pregnancies per female. These results do not support previous laboratory studies indicating that exposure to strangers causes pregnancy disruption and (or) infanticide at high rates. Therefore, in field conditions, little evidence was found indicating that female gray-tailed voles' reproductive fitness declines after exposure to strangers. I propose that results from laboratory studies on behavioral aspects of mammals should be validated with field data prior to being extrapolated to natural populations and applied to evolutionary paradigms

Metallo-organic ensembles of tritopic subphthalocyanine ligands

"This is the peer reviewed version of the following article: M. Ángel Revuelta-Maza, Ettore Fazio, Gema de la Torre and Tomás Torres, Metallo-organic ensembles of tritopic subphthalocyanine ligands, Journal of Porphyrins and PhthalocyaninesVol. 21, No. 12, pp. 782-789 (2017), which has been published in final form at https://doi.org/10.1142/S1088424617500882I. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use Self-Archived Versions"Organic building blocks containing amines and aldehydes can be used for the preparation of complex metallo-organic structures, such as M2L3 triple helicates or face-capped M4L4 tetrahedral cages, through the formation of both dynamic covalent and coordinative linkages during the self-Assembly process. Herein we describe how the subcomponent self-Assembly method can be succesfully applied over a triamine-functionalized subphthalocyanine (SubPc) ligand to build metallo-supramolecular helicates. Two isomeric SubPcs (C1-SubPc1 and C3-SubPc1) have been prepared from the corresponding C1-SubPcI3 and C3-SubPcI3 precursors under optimized Suzuki conditions. We selected the tritopic C3-SubPc1 derivative as ligand for the subcomponent self-Assembly experiments, which involved the reaction with 2-formylpyridine and different Fe(II) salts. The self-Assembly process was mainly studied by mass spectrometry (ESI direct injection techniques), and in all the conditions applied, we could observe the formation of helicate-Type Fe2SubPc3 structures and/or Fe2SubPc4 species, which can be considered as open precursors of Fe4SubPc4 tetrahedral cages. © 2017 World Scientific Publishing Company.Financial support from Comunidad de Madrid, Spain (S2013/MIT- 2841, FOTOCARBON), and Spanish MICINN (CTQ2014-52869-P) is acknowledged

Protection of outbred mice against a vaginal challenge by a Chlamydia trachomatis serovar E recombinant major outer membrane protein vaccine is dependent on phosphate substitution in the adjuvant.

Chlamydia trachomatis is the most common bacterial sexually-transmitted pathogen for which there is no vaccine. We previously demonstrated that the degree of phosphate substitution in an aluminum hydroxide adjuvant in a TLR-4-based C. trachomatis serovar E (Ser E) recombinant major outer membrane protein (rMOMP) formulation had an impact on the induced antibody titers and IFN-γ levels. Here, we have extended these observations using outbreed CD-1 mice immunized with C. trachomatis Ser E rMOMP formulations to evaluate the impact on bacterial challenge. The results confirmed that the rMOMP vaccine containing the adjuvant with the highest phosphate substitution induced the highest neutralizing antibody titers while the formulation with the lowest phosphate substitution induced the highest IFN-γ production. The most robust protection was observed in mice vaccinated with the formulation containing the adjuvant with the lowest phosphate substitution, as shown by the number of mice with positive vaginal cultures, number of positive cultures and number of C. trachomatis inclusion forming units recovered. This is the first report showing that vaccination of an outbred strain of mice with rMOMP induces protection against a vaginal challenge with C. trachomatis