Effect of Age and Vaccination on Extent and Spread of Chlamydia pneumoniae Infection in C57BL/6 Mice

BACKGROUND: Chlamydia pneumoniae is an obligate intracellular respiratory pathogen for humans. Infection by C. pneumoniae may be linked etiologically to extra-respiratory diseases of aging, especially atherosclerosis. We have previously shown that age promotes C. pneumoniae respiratory infection and extra-respiratory spread in BALB/c mice. FINDINGS: Aged C57BL/6 mice had a greater propensity to develop chronic and/or progressive respiratory infections following experimental intranasal infection by Chlamydia pneumoniae when compared to young counterparts. A heptavalent CTL epitope minigene (CpnCTL7) vaccine conferred equal protection in the lungs of both aged and young mice. This vaccine was partially effective in protecting against C. pneumoniae spread to the cardiovascular system of young mice, but failed to provide cardiovascular protection in aged animals. CONCLUSIONS: Our findings suggest that vaccine strategies that target the generation of a C. pneumoniae-specific CTL response can protect the respiratory system of both young and aged animals, but may not be adequate to prevent dissemination of C. pneumoniae to the cardiovascular system or control replication in those tissues in aged animals

A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C

Rabies, caused by RNA viruses in the Genus Lyssavirus, is the most fatal of all infectious diseases. This neglected zoonosis remains a major public health problem in developing countries, causing the death of an estimated 25,000-159,000 people each year, with more than half of them in children. The high incidence of human rabies in spite of effective vaccines is mainly linked to the lack of compliance with the complicated administration schedule, inadequacies of the community public health system for local administration by the parenteral route and the overall costs of the vaccine. The goal of our work was the development of a simple, affordable and effective vaccine strategy to prevent human rabies virus infection. This next generation vaccine is based on a replication-defective chimpanzee adenovirus vector belonging to group C, ChAd155-RG, which encodes the rabies glycoprotein (G). We demonstrate here that a single dose of this vaccine induces protective efficacy in a murine model of rabies challenge and elicits strong and durable neutralizing antibody responses in vaccinated non-human primates. Importantly, we demonstrate that one dose of a commercial rabies vaccine effectively boosts the neutralizing antibody responses induced by ChAd155-RG in vaccinated monkeys, showing the compatibility of the novel vectored vaccine with the current post-exposure prophylaxis in the event of rabies virus exposure. Finally, we demonstrate that antibodies induced by ChAd155-RG can also neutralize European bat lyssaviruses 1 and 2 (EBLV-1 and EBLV-2) found in bat reservoirs

Correction: A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C.

[This corrects the article DOI: 10.1371/journal.pntd.0008459.]

Further characterization of interactions between gamete surface antigens of Plasmodium falciparum

Target antigens of malaria transmission blocking immunity include a complex of 3 gamete surface proteins of 230-kDa and 48/45-kDa glycoproteins. Previous studies have shown that epitopes recognized by blocking antibodies are conformational (reduction sensitive) in nature. Studies were conducted to characterize the interactions between the target antigens and role of disulfide groups in the formation of the complex. Treatment of detergent extracts of gametes with chaotropic agents and extremes of pH resulted in dissociation of the complex. The interaction between the 3 proteins was also perturbed when the extract was incubated in the presence of antibodies against the 230-kDa protein but not against the 48/45-kDa doublet. Chemical modifications of disulfide and sulfhydryl groups in the target antigens, otherwise inaccessible either in the total extract or after phase separation in Triton X-114, required prior denaturation of antigens. © 1992

Mapping of two overlapping linear epitopes in Pfg27 recognized by Plasmodium falciparum transmission-blocking monoclonal antibodies

We have reported previously the production of Plasmodium falciparum transmission-blocking monoclonal antibodies (mAb) recognizing a reduction-insensitive cross-reacting epitope in the gametocyte antigen Pfg27 and the gamete surface antigens Pfs230 and Pfs48 45. In this study, the amino acid sequence of this epitope in Pfg27 was determined. First, the epitope was localized near the N terminus of the protein by probing recombinant overlapping fragments spanning Pfg27 with transmission-blocking mAb in immunoblot experiments. The amino acid sequence of the epitope was then determined by using overlapping synthetic peptides spanning the smallest immunoreactive recombinant fragment in an ELISA. The sequence KPLDKFGNIYDYHYEH (amino acids 10-25 in the Pfg27 sequence) was shown to contain two overlapping epitopes recognized by transmission-blocking mAb. Comparison of the sequence of the gene encoding Pfg27 in seven different P. falciparum strains demonstrated that these sequential epitopes are totally conserved. Immunization of mice with synthetic peptides derived from Pfg27, conjugated with keyhole limpet hemocyanin (KLH) and formulated in Freund\u27s adjuvant or alum, resulted in the production of antibodies capable of recognizing the peptides as well as the native Pfg27. © 1995

Amastigote surface proteins of Trypanosoma cruzi are targets for CD8+ CTL

Amastigotes of Trypanosoma cruzi express surface proteins that, when released into the host cell cytoplasm, are processed and presented on the surface of infected cells in the context of MHC class I molecules to be recognized by CD8+ CTL. To further understand the role of CTL in T. cruzi infection, we used the available MHC class I peptide binding motifs to identify potential CTL target epitopes in two recently described T. cruzi amastigote surface proteins, ASP-1 and ASP-2. The predicted amino acid sequences of ASP-1 and ASP-2 were screened for H-2b allele-specific class I peptide motifs, and four peptides (PA11, PA12, PA13, and PA14) and six peptides (PA5, PA6, PA7, PA8, PA9, and PA10) were synthesized from ASP-1 and ASP-2, respectively. The majority of the peptides bound to some degree to H-2b class I MHC molecules, and six of 10 of the peptides stimulated spleen cells from T. cruzi-infected mice to lyse target cells sensitized with the homologous peptides. Short term T cell lines specific for three of these peptides also lysed T. cruzi-infected target cells. These results demonstrate that ASP-1 and ASP-2 are targets of in vivo generated CTLs and that this CTL response induced by T. cruzi infection is parasite and peptide specific, MHC restricted, and CD8 dependent