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Simple Summary: To investigate whether the influenza virus infection affects the reproduction and transmission of Toxoplasma gondii, we attempted to identify the specific influencing factors. In this study, we found that decreased expression levels of IL-1β, IL-6, and IL-12 in the co-infected group were associated with the early immune responses of the host against T. gondii type II strain (Pru), which affected the division of T. gondii (Pru). Moreover, the significant decrease in the CD4+/CD8+ ratio indicated a weakened long-term immune killing ability of the host against T. gondii (Pru) after IAV infection. In conclusion, our study showed that a mixed infection of IAV (influenza A virus) virus and T. gondii (Pru) co-infection was lethal in mice and that the two pathogens may act synergistically. This study aimed to investigate the relationship between the T. gondii type II strain (Pru) and respiratory viral infections, specifically focusing on the co-infection with PR8 (influenza A/Puerto Rico/8/34). In this study, we found that the number of T. gondii (Pru) in the lungs of co-infected mice was significantly higher and lesions were more severe than those in the group infected with T. gondii (Pru) alone, whereas IAV (influenza A virus) copy numbers of co-infected and PR8 alone infected groups were negligible, suggesting that infection with IAV increased the pathogenicity of T. gondii (Pru) in mice. The invasion and proliferation assays demonstrated no significant effect of co-infection on T. gondii (Pru) infection or replication in vitro. To further explore the factors causing the altered pathogenicity of T. gondii (Pru) caused by co-infection, we found that decreased expression levels of IL-1β, IL-6, and IL-12 in the co-infected group were associated with the early immune responses against T. gondii (Pru), which affected the division of T. gondii (Pru). Moreover, the significant decrease in the CD4+/CD8+ ratio indicated a weakened long-term immune killing ability of the host against T. gondii (Pru) following IAV infection. In conclusion, a T. gondii type II strain (Pru) could not be properly cleared by the host immune system after IAV infection, resulting in toxoplasmosis and even death in mice. [ABSTRACT FROM AUTHOR]

Background: We report long-term safety and immunogenicity of Takeda's tetravalent dengue vaccine candidate (TAK-003) in healthy children and adults living in dengue-endemic areas in Puerto Rico, Columbia, Singapore, and Thailand.Methods: In part 1 of this phase 2, randomized, placebo-controlled trial we sequentially enrolled 1.5-45 year olds (n = 148) into 4 age-descending groups, randomized 2:1 to receive 2 doses of TAK-003 or placebo 90 days apart. In part 2, 1-11 year olds (n = 212) were enrolled and randomized 3:1 to TAK-003 or placebo groups. We assessed neutralizing antibody titers for the 4 dengue serotypes (DENV) up to month 36 in part 1, and symptomatic dengue and serious adverse events (SAEs) up to month 36 in both parts.Results: At month 36, seropositivity rates were 97.3%, 98.7%, 88.0% and 56.0% for DENV-1, -2, -3 and -4, respectively. Seropositivity rates varied significantly for DENV-4 according to serostatus at baseline (89.5% in seropositives versus 21.6% in seronegatives). No vaccine-related SAEs were reported.Conclusions: The trial demonstrated persistence of neutralizing antibody titers against TAK-003 over 3 years in children and adults living in dengue-endemic countries, with limited contribution from natural infection. TAK-003 was well tolerated.Clinical Trials Registration: NCT01511250. [ABSTRACT FROM AUTHOR]

A primary challenge in developing effective vaccines against obligate, intracellular, bacterial tick-borne pathogens that establish persistent infection is the identification of antigens that cross protect against multiple strains. In the case of Anaplasma marginale, the most prevalent tick-borne pathogen of cattle found worldwide, OmpA is an adhesin and thus a promising vaccine candidate. We sequenced ompA from cattle throughout Ghana naturally infected with A. marginale in order to determine the degree of variation in this gene in an area of suspected high genetic diversity. We compared the Ghanaian sequences with those available from N. America, Mexico, Australia and Puerto Rico. When considering only amino acid changes, three unique Ghanaian OmpA variants were identified. In comparison, strains from all other geographic regions, except one, shared a single OmpA variant, Variant 1, which differed from the Ghanaian variants. Next, using recombinant OmpA based on Variant 1, we determined that amino acid differences in OmpA in Ghanaian cattle as compared to OmpA Variant 1 did not alter the binding capacity of antibody directed against OmpA Variant 1, supporting the value of OmpA as a highly conserved vaccine candidate. [ABSTRACT FROM AUTHOR]