Naturally acquired human immune responses against Helicobacter pylori and implications for vaccine development PrefaceHelicobacter pylori has been identified as a causative agent of gastroduodenal pathology. Vaccination studies with mouse models have shown that immunisation with bacterial antigens can provide protection against infection, indicating that it may be possible to design vaccines which terminate colonisation by H pylori or prevent it from taking place. Here, we review critically current knowledge of naturally acquired human humoral and cellular immune responses to H pylori with the aim of delineating questions which should be tackled in order to permit a rational and directed approach to the development of an eVective vaccine. We have also reviewed the literature and identified candidate vaccine antigens.

The progress toward subunit vaccines has been limited by their poor immunogenicity and limited stability. To enhance the immune response, subunit vaccines universally require improved adjuvants and delivery vehicles. In the present paper, we propose the use of cross-linked protein crystals (CLPCs) as antigens. We compare the immunogenicity of CLPCs of human serum albumin with that of soluble protein and conclude that there are marked differences in the immune response to the different forms of human serum albumin. Relative to the soluble protein, crystalline forms induce and sustain over almost a 6-month study a 6-to 10-fold increase in antibody titer for highly cross-linked crystals and an approximately 30-fold increase for lightly cross-linked crystals. We hypothesize that the depot effect, the particulate structure of CLPCs, and highly repetitive nature of protein crystals may play roles in the enhanced production of circulating antibodies. Several features of CLPCs, such as their remarkable stability, purity, biodegradability, and ease of manufacturing, make them highly attractive for vaccine formulations. This work paves the way for a systematic study of protein crystallinity and cross-linking on enhancement of humoral and T cell responses.