Immunogens and Antigen Processing: Report from a Global HIV Vaccine Enterprise Working Group

The Global HIV Vaccine Enterprise convened a meeting of a Working Group in July 2009 to discuss recent progress in rational design of the components of an HIV vaccine, such as inserts, vectors and adjuvants,and in understanding antigen processing and presentation to T and B cells. This Report summarizes the key points of that discussion, and subsequent discussions with the Chairs of the other Enterprise Working Groups, the Enterprise Science Committee, the Enterprise Council and the broader scientific community during open sessions at scientific conferences

Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin

Immunological effects of feeding different sources of vitamin E and seaweed in a sheep herd during the winter season

In winter fed organic raised sheep inadequate plasma vitamin E levels is common and therefore supplementation is recommended. The objective of the present work was to test the supplementation of natural vitamin E and seaweed meal on the immune status of ewes and their offspring. Forty Norwegian White Sheep ewes were randomly allocated to three supplementation treatments: natural vitamin E, synthetic vitamin E, seaweed meal, and control. The feeding experiment lasted the entire indoor feeding period. Ewes and newborn lambs were vaccinated against different environmental microorganisms and pathogens. Different immunological parameters were measured. Supplementing the ewes with natural vitamin E had positive effect on immunity against Mycobacterium bovis in lambs. Seaweed, on the other hand, had negative effect on the passive transfer of maternal antibodies in lambs the first week after birth. The adaptive immunity was not affected by seaweed supplementation

Characterization, cloning and immunogenicity of antigens released by transforming cercariae of Schistosoma mansoni

A schistosome infection is initiated when the parasite penetrates the skin of a susceptible host. Relatively large quantities of protein are released by transforming cercariae compared to later larval stages. This represents the first parasite material to which the host's immune system is exposed, yet little is known about the proteins which are released during the first few hours post-transformation. We have shown that antiserum raised against such molecules was capable of imparting protection against a schistosome challenge infection upon passive transfer to naïve mice. By screening a cercarial cDNA library with this serum, 38 positive clones were identified. Sequence analysis showed these to represent 8 different molecules which included Schistosoma mansoni 21·7 kDa antigen, calcium-binding-protein and the vaccine candidate glutathione S-transferase (Sm28GST). In addition, 5 clones were isolated, 1 of which had significant homology to many cytochrome C proteins, another with leukocyte elastase inhibitors and 3 which represented novel molecules. Four clones were expressed in a prokaryotic high-level expression vector, sera produced against each purified recombinant protein and used subsequently to probe Western blots and parasite sections. The leukocyte elastase inhibitor homologue and 2 unknowns induced significant proliferation by lymph node cells recovered from mice vaccinated with irradiated cercariae. More strikingly, the 2 novel proteins stimulated very high levels of interferon [gamma] (IFN[gamma]) secretion both by lymph node cells and those recovered by broncho-alveolar lavage from the lungs of vaccinated mice. Such results will be discussed in the context of vaccine development

Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein

Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcRI and FcRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection

Passive immunization against Histomonas meleagridis does not protect turkeys from an experimental infection

Histomonosis or blackhead is a disease of gallinaceous birds, caused by the protozoan Histomonas meleagridis. As recent regulatory action has removed almost all drugs against this disease from the European market, the development of new prophylactics has become crucial. Identification of the protective immune mechanism would facilitate the choice and development of a vaccination strategy to prevent histomonosis. In this study, turkeys were either actively or passively immunized and were then challenged to assess the role of antibody-mediated immunity in the protection form this disease. Active immunization was performed either by experimental infection and treatment or by intramuscular injection with lysed H. meleagridis. Passive immunization was attempted by intraperitoneal administration of pooled, concentrated, neutralizing antisera from immunized donor animals to naive turkeys. A significantly higher IgG response was observed after infection and treatment than after intramuscular injection, which in turn was higher than the responses of placebo and control birds. While active immunization of turkeys by intramuscular injection of dead H. meleagridis antigens appeared not to be protective against histomonosis, immunization by infection and treatment did induce protection. However, no significant level of protection could be observed in the passively immunized birds. These results suggest that serum antibodies to H. meleagridis may not be a key component in the protection against this parasite. It is, however, possible that the concentration of antibodies at the mucosal site is insufficient. Therefore, further investigation on mucosal immune responses is necessary