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BackgroundBCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis (TB). We tested BCG (SSI1331) (in 6 animals, delivered intradermally) and a recombinant (rBCG) AFRO-1 expressing perfringolysin (in 6 animals) followed by two boosts (delivered intramuscullary) with non-replicating adenovirus 35 (rAd35) expressing a fusion protein composed of Ag85A, Ag85B and TB10.4, for the capacity to induce antigen-specific cellular immune responses in rhesus macaques (Macaca mulatta). Control animals received diluent (3 animals).Methods and FindingsCellular immune responses were analyzed longitudinally (12 blood draws for each animal) using intracellular cytokine staining (TNF-alpha, IL-2 and IFN-gamma), T cell proliferation was measured in CD4+, CD8alpha/beta+, and CD8alpha/alpha+ T cell subsets and IFN-gamma production was tested in 7 day PBMC cultures (whole blood cell assay, WBA) using Ag85A, Ag85B, TB10.4 recombinant proteins, PPD or BCG as stimuli. Animals primed with AFRO-1 showed i) increased Ag85B-specific IFN-gamma production in the WBA assay (median >400 pg/ml for 6 animals) one week after the first boost with adenoviral-delivered TB-antigens as compared to animals primed with BCG (<200 pg/ml), ii) stronger T cell proliferation in the CD8alpha/alpha+ T cell subset (proliferative index 17%) as compared to BCG-primed animals (proliferative index 5% in CD8alpha/alpha+ T cells). Polyfunctional T cells, defined by IFN-gamma, TNF-alpha and IL-2 production were detected in 2/6 animals primed with AFRO-1 directed against Ag85A/b and TB10.4; 4/6 animals primed with BCG showed a Ag85A/b responses, yet only a single animal exhibited Ag85A/b and TB10.4 reactivity.ConclusionAFRO-1 induces qualitatively and quantitatively different cellular immune responses as compared with BCG in rhesus macaques. Increased IFN-gamma-responses and antigen-specific T cell proliferation in the CD8alpha/alpha+ T cell subset represents a valuable marker for vaccine-take in BCG-based TB vaccine trials

We isolated Sindbis virus (SINV) from the enzootic mosquito vectors Culex torrentium, Cx. pipiens, and Culiseta morsitans collected in an area of Sweden where SINV disease is endemic. The infection rate in Cx. torrentium mosquitoes was exceptionally high (36 infections/1,000 mosquitoes), defining Cx. torrentium as the main enzootic vector of SINV in Scandinavia.

The authors discuss the morbidity associated with viridans streptococcus bacteremia, and its implications on the choice of antibiotics used as prophylaxis and treatment. They retrospectively studied the case notes of 38 children who were being treated for various malignant conditions in their unit and developed 40 episodes of bacteremia with viridans streptococci between October 1995 and January 1999. Viridans streptococci were the third commonest blood culture isolate during this period, after coagulase-negative staphylococci and Staphylococcus aureus. The majority of the isolates were Streptococcus mitis (55%). Others were S. sanguis (25%), S. oralis (12.5%), S. salivarius (5%), and S. acidominimus (2.5%). Twenty-five percent of the patients had been treated with regimens that included cytosine arabinoside, 60% were receiving prophylactic co-trimoxazole, and 87.5% were neutropenic. Thirty percent of patients had abnormal chest X-rays, and 15% were hypotensive; 2 patients required admission to the intensive care unit. Initial antibiotic therapy was changed because of failure of clinical response in 60% of cases, despite the infecting organism being sensitive in vitro. This study confirms the importance of viridans streptococci as a cause of bacteremia in pediatric hematology and oncology patients, leading to significant morbidity. Further work is required to establish the optimal treatment for viridans streptococcus bacteremia.

Simian immunodeficiency virus (SIV) uses the CCR5 chemokine receptor as the main co-receptor to enter CD4 M cells. RANTES, MIP-1α and MIP-1β have been suggested as the major human immunodeficiency virus-suppressor factors produced by CD8 M T-cells. The aim of this study was to investigate the CD8 M T-cell production of anti-viral factors and of β-chemokines in six cynomolgus macaques vaccinated with live attenuated SIVmacC8 in relation to protection against infectious intrarectal SIVsm challenge. Three of the vaccinated animals were completely protected and one was partially protected against the challenge virus. Interestingly, these monkeys showed higher in vitro anti-viral CD8 M cell suppressor activity and β-chemokine production both before and after vaccination as compared to the infected monkeys. The results indicate that β-chemokines may play a role in protective immunity but also that genetic and/or environmental factors may influence their production.