The first session addressed the genetic host factors that could influence the immune responses against different pathogens. Dr. Thomas Hawn (University of Washington School of Medicine, USA) discussed about the limitations of the treatment against tuberculosis caused by the partial protection conferred by the Bacillus Calmette-Guerin (BCG) vaccine and the poor understanding of the mechanism of immunity to Mycobacterium tuberculosis (Mtb). In this regard, the study of the possible host genetic factors, probably linked to the inadequate immune response, was examined. Innate immune genes appeared to be associated to altered in vivo responses to BCG and its clinical efficacy. Whole blood cells of South African newborns were stimulated ex vivo with BCG, ten weeks after vaccination, and a defined innate immune pathway polymorphism was found to be associated to T cell cytokines responses and susceptibility to tuberculosis. This finding provided evidence on the correlation between innate and adaptive responses after in vivo vaccination and has important implications for novel vaccine strategies and IFN-γ based diagnosis for tuberculosis.

Meanwhile, Dr. Mary Carrington (Frederick National Lab, USA) presented results on the influence of the differential expression levels of HLA class I for HIV control. They showed that a polymorphic microRNA target site in the 3´ untranslated region (3´-UTR) of HLA-C regulates binding of miR-148a and posttranscriptional processing, which generates different expression levels of HLA-C. They determined that this expression has a direct effect in the HIV infection outcomes. Other genes like those of natural killer immunoglobulin- and leukocyte immunoglobulin-like receptors could be implicated in this process and have an impact on host defence against the virus. The concept of system vaccinology and its potential impact on the vaccine field was discussed by Dr. Bali Pulendran Emory Vaccine Center, USA in the second day. The role of innate immune system in tuning immune responses and the identification of molecular signatures induced immediately after vaccination which correlate with later development of protective responses were presented as crucial for the understanding of vaccine efficacy. The examples of the use of Systems Biology in yellow fever vaccine YF-17D and influenza vaccines were reviewed.Similarly, Dr. Alan Aderem (Seattle Biomedical Research Institute, USA) analyzed the different approaches that had been used until now in vaccines discovery and how Systems Biology provide new tools to address the complexity of the immune system and for a more rational vaccine design. Taken together, both conferences showed the potential of this recent development to speed up not only the vaccine candidate discovery, but also the streamline of vaccines’ research, manufacturing and clinical trials.

Taking advantage of new mass cytometry methodology, Dr. Mark M. Davis and colleagues (Stanford University, USA) analyzed the response to influenza vaccination in humans. They developed a method to screen blood samples for over 100 peptide-MHC tetrameters at once using combinatorial labelling of cells with many more colors than in fluorescence based analysis. In this case, they used a panel of 34 flu-peptide-class II MHC tetrameters together with CD25+ phenotypic and functional markers and find good correlation between the flu epitope specific T CD4+ response and both antibody titers and CD8+ T cell responses.

Two studies exemplified the use of the high-content genome analysis in vaccine research, presented by Dr. Danilo Casimiro (Merck Research Laboratories, USA). In one study, RNA expression profile analysis in response to marketed vaccines revealed a gene module associated with adverse effects as documented in published results. The second identified host biomarkers for hypo-responsiveness to vaccination in elderly, in a cohort of 140 65-years-old adults with several vaccines for both recall (tetanus-diphtheria booster, hepatitis A virus) and de novo responses (hepatitis B surface antigen; HBsAg).

Dr. Scott D. Boyd (Stanford University, USA) versed on throughput DNA sequencing of antibody gene rearrangement after an influenza vaccination. His team characterized B cell clonal expansions with that approach, combined with both single cell cloning and the expression of antibodies specific to vaccine antigens, to provide new insights on the B cell lineages responding to vaccination. Strikingly, although vaccines showed particular sequence family convergent antibody gene rearrangements, different at DNA level, they are highly similar at protein level and correlated with seroconversion. So, consistent molecular features in response to vaccination could be defined regardless of the individual gene repertoire differences found.

Dr. Antonio Lanzavecchia (Institute of Research in Biomedicine, Switzerland) delivered a lecture on the human memory B and plasma cells. His team was able to isolate unusually potent neutralizing antibodies against the human cytomegalovirus from infected donors. Their respective viral ligands were then identified and used to design an experimental vaccine. This technique was also applied to identify antibodies against pan-influenza A that neutralized conserved regions of both RSV and metapneumovirus.

Additionally, Dr. Hana Golding (Center for Biologics Evaluation and Research, USA) used whole-genome-fragment phage display libraries and surface plasmon resonance technologies to understand humoral responses against influenza vaccines. It was found that MF59 and AS03 adjuvants induce epitope spreading from hemagglutinin HA2 to HA1 and to neuroaminidase, compared to non- or aluminium-adjuvanted vaccines. Broadening cross-clade neutralization correlated with 2-3 fold increases in antibodies avidity to properly folded HA1.

The concept of reverse vaccinology was addressed by Dr. Rhea N. Coler (Infectious Disease Research Institute, USA) for tuberculosis antigen discovery. A panel of approximately 100 genes of Mtb, including those related to its growth in macrophages, up or downregulation under hypoxic conditions, secretion, membrane association o members of the PE/PPE or Esx families, were studied. The corresponding recombinant proteins were evaluated for IFN-γ recall responses in healthy subjects previously exposed to Mtb, to identify dominant T cell antigens in humans. Antigens conferring protection in mice against Mtb were selected and expressed as fusion molecules. One of these proteins, ID93, was shown to confer both prophylactic and therapeutic protection against tuberculosis in mice, guinea pigs and non-human primate models. The remarkable topic of immunology of vaccination in young and the elderly was also discussed in several conferences. Dr. Jorg J. Goronzy (Stanford University and the Veterans Affairs Palo Alto Health Care System, USA) presented a work in which, by using a bioinformatic tool, his team found that the repertoire diversity of T cells is very robust regardless the age-related thymic involution. This contrast with the previous and well accepted idea that this last factor led to a contraction in the repertoire could severely limit the ability to recognize antigens, which only can be overcome by thymic rejuvenation. Other negative signals that affect immunological functions of T cells had also been described and become important pharmacological targets to restore T cells defects in elderly. For example, a negative feedback loop that curtails the nuclear activity of ERK and JNK kinases could be counterbalanced by silencing the controller DUSP4 expression in elderly CD4+ T cells, restoring their helper activity for B cells differentiation and antibody production.

In an interesting talk, Dr. Bonnie B. Blomberg (University of Miami Miller School of Medicine, USA) addressed the issue of biomarkers of vaccine efficacy in elderly. She showed that aged B cells secrete increased levels of TNF-α and this correlates with their decreased function. This rise in the proinflammatory status (increased levels of TNF-α, IL-6, C-reactive protein, and CMV replication) could directly impact in B cell function, thus impairing the capacity of individuals to respond to vaccination. Differences like those in immune responses in elderly could be assessed by an in vitro system proposed by Dr. Ofer Levy (Boston Children’s Hospital and Harvard Medical School, USA). A novel human microphysiologic assay system was developed, using primary newborn, infant and adult leukocytes cultured in autologous plasma containing soluble factors that vary with age and exert deep effects on the magnitude and nature of immune responses.

Taken together all the results presented led to a better and hopeful understanding of immune responses mechanisms triggered by vaccination, which was further complemented by the intense discussion generated during poster sessions.

POSTER SESSIONS