Elicitation of predictable immune responses by using live bacterial vectors.

There is an increasing need for novel vaccines able to stimulate efficient and long-lasting responses, which have also low production costs. To confer protective immunity following vaccination, the adequate type of response should be elicited. Vaccines based on attenuated bacterial carriers have contained production and delivery costs, and are able to stimulate more potent immune responses than non-replicating formulations. The improved knowledge on carrier physiology and host response, the availability of different mutants and highly sophisticated expression tools, and the possibility of co-administering modulators enable to trigger predictable responses according to the specific needs. Recent studies support the use of attenuated bacteria not only as conventional carriers, but also as a delivery system for DNA vaccines against infectious agents and tumors. In this review we discuss the most widely used bacterial carrier systems for either antigens or nucleic acid vaccines, and the strategies which have been successfully exploited to modulate the immune responses elicited.

Prenatal immune priming in onchocerciasis-onchocerca volvulus-specific cellular responsiveness and cytokine production in newborns from infected mothers.

This study investigated the effect of maternal Onchocerca volvulus infection on humoral and cellular responsiveness in newborn children and their mothers. Onchocerca volvulus-specific IgG isotypes and IgE were significantly elevated in infected mothers and their infants. One year post partum, O. volvulus-specific IgG4 was strongly reduced in children of infected mothers, while IgG1 responses weakened only slightly. Umbilical cord mononuclear blood cells (UCBC) and peripheral blood cells (PBMC) from mothers proliferated in response to phytohaemagglutinin (PHA), concanavalin A (Con A), and the bacterial antigens streptolysin-O (SL-O) or purified protein derivative (PPD). UCBC from neonates born to O. volvulus-infected mothers responded lower (P < 0.01) to Con A (at 5 micrograms/ml), PPD (at 10 and 50 micrograms/ml) and O. volvulus-derived antigens (OvAg) (at 35 micrograms/ml), and in parallel, a diminished cellular reactivity (P < 0.01) by PBMC was observed to OvAg in mothers positive for O. volvulus. Several Th1-type (IL-2, IL-12, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)) and Th2-type (IL-4, IL-5, IL-10, IL-13) cytokines were secreted by UCBC and PBMC in response to OvAg, bacterial SL-O and PHA. OvAg did not stimulate IL-2 and none of the mitogens or antigens induced production of IL-4 in neonates. In response to OvAg, substantially elevated (P < 0.01) amounts of IFN-gamma were produced by UCBC from newborns of O. volvulus-infected mothers. UCBC secreted low levels of IL-5 and IL-13, while higher amounts of IL-10 were found (P < 0. 01) in newborns from onchocerciasis-free mothers. In conclusion, maternal O. volvulus-infection will sensitize in utero parasite-specific cellular immune responsiveness in neonates and activate OvAg-specific production of several Th1- and Th2-type cytokines.