Analysis of the immune response of a new malaria vaccine based on the modification of cryptic epitopes

Abstract

Malaria is a severe, life-threatening infectious disease that endangers human health. However, there are no vaccines or immune strategy of vaccines succeeding in both erythrocytic and pre-erythrocytic stage. During the liver stage of the Plasmodium life cycle, sporozoites invade the host liver cells. The sporozoites, then, induce a cellular immune response via the major histocompatibility complex (MHC) molecules on their surfaces. The cytotoxic T lymphocytes (CTLs) then recognize the corresponding antigen-MHC complex on the surfaces of these infected liver cells and kill them. However, dominant epitopes with high MHC affinity are prone to mutation due to immune selection pressure. CTLs evoked by the original dominant epitopes cannot recognize the mutated epitopes, leading to immune evasion. In this study, we have modified the cryptic epitopes of different antigens in the sporozoite and liver stages of Plasmodium falciparum to increase their immunogenicity without changing T cell antigen receptor (TCR)-peptide binding specificity. In addition, we have also added an important erythrocytic phase protective antigen, named apical membrane antigen 1 (AMA-1), to this process with the goal of constructing a complex multi-stage, multi-epitope recombinant DNA vaccine against P. falciparum. The vaccine was tested in HHD-2 mice. The method involved multiple stages of the P. falciparum life cycle as well as elucidation both humoral and cellular immunity. The conclusion drawn from the study was that the vaccine might provide an important theoretical and practical basis for generating effective preventative or therapeutic vaccine against P. falciparum.

Identification of a Continuous Neutralizing Epitope within UL128 of Human Cytomegalovirus

“…In addition, the observation that antibodies in HCMV ϩ individuals react only minimally with peptides containing the 13B5 target sequence may suggest that this sequence is only minimally immunogenic or only rarely recognized by the immune system during natural HCMV infection, which is consistent with characteristics of an immunologically "cryptic" epitope (45). Epitope crypticity is a common pattern of immune evasion and has been described for many other pathogens such as HIV, influenza virus, dengue virus, Plasmodium falciparum, and Bacillus anthracis (45)(46)(47)(48)(49). While it appears contradictory how the 13B5 epitope can be immunologically cryptic and at the same time a target of potent NAb, this could be explained by differences in the accessibility of the 13B5 binding site during natural HCMV infection.…”