PubMed · 14063523
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M H SMITH. 1963. ACTIVE IMMUNIZATION: CURRENT CONSIDERATIONS.. https://pubmed.ncbi.nlm.nih.gov/14063523/
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Among measles unvaccinated infants in Guinea-Bissau, we tested whether case infants with acute lower respiratory tract infection (ALRI), especially ALRI caused by respiratory syncytial virus (RSV), were more likely to be Bacille Calmette Guerin (BCG)-unvaccinated and to have no scar after BCG vaccination than were control infants without symptoms of ALRI. Three hundred and eighty-six case infants with ALRI were identified at a paediatric clinic (N=84), a health centre (N=82), and in a community morbidity surveillance system (N=220). Control infants were matched on sex, age, and district and were also measles unvaccinated. In ALRI case infants, the adjusted OR of being BCG unvaccinated was 2.87 (1.31-6.32), 1.72 (0.48-6.19) in boys and 4.45 (1.48-13.4) in girls. Among BCG vaccinated ALRI case infants, the adjusted OR of having no BCG scar was 1.54 (0.86-2.75), 0.93 (0.45-1.91) in boys and 2.70 (1.21-6.02) in girls. In ALRI case infants with RSV infection, similar trends were observed. BCG vaccination may have a non-targeted protective effect against ALRI, the effect being most marked in girls.
BACKGROUND: There is a need to develop an improved anti-TB vaccine for adequate control and elimination of tuberculosis, to control the spread of MDR-TB and TB/HIV co-infection. Studies in children have indicated that BCG vaccination has certain beneficial effects, especially against miliary TB and TB meningitis, but needs to be improved for protection against pulmonary tuberculosis. OBJECTIVE: The aim of the present study was to identify the immunogenic proteins in the culture filtrate (CF) of Mycobacterium bovis BCG by studying the effector mechanism of protection in children, which may help in the formulation of an effective vaccine against tuberculosis. MATERIALS AND METHODS: Lymphoproliferative responses (LTT) and the levels of IL-2 and IFN-gamma (Th1 cytokines) released into the culture supernatants were estimated (by ELISA) in short-term cultures of PBMC of BCG vaccinated (n=25) and unvaccinated (n=15) children and children with tuberculosis (n=15) against 10 different fractions of CF (mol.wt > or = 90-<14 kDa). RESULTS: The mean stimulation indices (SI) in LTT against all the (10) fractions in vaccinated children were high when compared to the unvaccinated and diseased groups; however, of the 10 fractions, F3, F4, F6, F8 and F9 elicited significantly higher SIs than the other fractions (p<0.05). In the vaccinated children, the SI (5.58+/-1.57), levels of IL-2 (381.66+/-16.40 pg/ml) and IFN-gamma (732+/-62.36 pg/ml) in the cultures stimulated by fraction 8 (34-30k Da) were significantly higher (p<0.001), than responses to the other fractions and also to those of other groups of children. CONCLUSION: Thus, the peptides within the cluster 34-30 kDa appear to be promising vaccine candidates by virtue of their immunodominant nature specifically priming Th1 cells in normal, BCG-vaccinated children.
There is an urgent need for an improved vaccine against tuberculosis. Heterologous prime-boost immunization regimes induce higher levels of cellular immunity than homologous boosting with the same vaccine. Using BCG as the priming immunization in such a regime allows for the retention of the beneficial protective effects of BCG against disseminated disease in childhood. Recombinant poxviruses are powerful boosting agents, for both CD4+ and CD8+ T cells. Here we review the preclinical data from a BCG prime-recombinant modified vaccinia virus Ankara expressing antigen 85A (MVA85A) boost strategy. MVA85A is now in clinical trials in the UK and Africa and the design of these trials, including the ethical and regulatory issues are discussed.