Neonatal mycobacterial specific cytotoxic T‐lymphocyte and cytokine profiles in response to distinct BCG vaccination strategies

Abstract

SUMMARYThis study evaluated whether different bacillus Calmette±Gue Ârin (BCG) strains, routes of administration, vaccination age and percutaneous tools in¯uenced immune responses to BCG vaccination in infants. Proliferative responses, cytokine production and cell-mediated cytotoxicity obtained in post-vaccinated children were compared to baseline cord bloods and unvaccinated 10-week-old infants. BCG vaccination generally induced strong lymphoproliferative and T helper type 1 (Th1)-type cytokine responses. There was a trend for greater responsiveness following the intradermal route of vaccination, with Japanese-172 strain and with delaying vaccination until 10 weeks. Cord mononuclear cells differentially stimulated the Th2-type cytokines interleukin-5 (IL-5) and IL-10 selectively in response to BCG, as compared to H37Rv or puri®ed protein derivative stimulation. We document for the ®rst time the generation of mycobacterium-speci®c cytotoxic T lymphocytes in neonates, following BCG vaccination. Cytotoxic activity correlated with the ratio of interferon-c to IL-5, aside from a single instance where use of the Biovac 1 tool resulted in a striking dissociation selectively against H37Rv targets. These data have implications for correlates of protective immunity in design of vaccine studies.

Vacina BCG: via percutânea ou intradérmica?

“…Adults who have been previously sensitized, exhibit a wide spectrum of reponses to a the various M. tuberculosis antigens. 49 These results, obtained in vitro, confirm the classic clinical findings that responses to BCG are accelerated when people who have been previously sensitized are vaccinated. 22,23,26,49 The BCG vaccine induces a Th1 and Th2 response, but, the action of cytotoxic lymphocytes is modulated by the cytokines that are produced by the Th1 lymphocytes.…”

“…49 These results, obtained in vitro, confirm the classic clinical findings that responses to BCG are accelerated when people who have been previously sensitized are vaccinated. 22,23,26,49 The BCG vaccine induces a Th1 and Th2 response, but, the action of cytotoxic lymphocytes is modulated by the cytokines that are produced by the Th1 lymphocytes. The results of recent studies, performed with both humans and animals, suggest that previous exposure to mycobacteria antigens is associated with increased cytotoxic activity and that, in order to be reliable, the BCG vaccine should be administered before the recipient has been exposed to M. tuberculosis or other mycobacteria.…”

“…47,48 It is believed that tuberculosis protection is more closely linked to IF-γ titers and to the titers of cytokines produced by Th2 lymphocytes than to the absolute titers of each cytokine. 49 The response to BCG varies according to previous mycobacteria sensitization. Tests performed in vitro have demonstrated that, among adults with a negative reaction to tuberculin testing, a response to soluble M. tuberculosis antigens appears a week after BCG administration; the response to antigens form the cell wall membrane only occurs 4 weeks post vaccination, coinciding with Mantoux test conversion and a response to antigens prepared by the cytolysis of M. tuberculosis appear a year after vaccination.…”

“…The results of recent studies, performed with both humans and animals, suggest that previous exposure to mycobacteria antigens is associated with increased cytotoxic activity and that, in order to be reliable, the BCG vaccine should be administered before the recipient has been exposed to M. tuberculosis or other mycobacteria. 39,43,49 Among adults, BCG induces a strong Th1 response, however, studies performed with laboratory animals have indicated that early exposure to bacterial antigens may induce a response that predominantly involves Th2 lymphocytes, which are more associated with hypersensitivity that with protective immunity. This fact is of great concern when it is remembered that the BCG vaccine is recommended for newborn babies.…”

“…49 Furthermore, children vaccinated at between 0 and 4 months with BCG-ID exhibit Th1 cell memory, maintaining high IF-g production and low IL 5 production. 50 The relationship between DTH skin test response and IF-γ γ γ γ γ production…”