Characterization of a branched lipopeptide candidate vaccine against influenza A/Puerto Rico 8/34 which is recognized by human B and T-cell immune responses

The use of synthetic peptides as immunogens represents an exciting alternative to traditional vaccines. However, to date most of these synthetic peptides are not highly immunogenic. The lack of immunogenicity might be addressed by conjugation between T or B cell epitopes with universal or immunodominant T-helper epitopes. The construction of lipidated peptides, branched peptides, or designs combining both of these elements might enhance the immunogenicity, as they might target Toll-Like Receptors and/or mimic the 3-dimensional structure of epitopes within the native protein. Herein, a recognized peptide immunogen based on the hemagglutinin protein of A/Puerto Rico/8/34 was chosen as a backbone and modified to evaluate if the construction of branched peptides, lipidation, the addition of cysteine residues, or mutations could indeed alter epitope reactivity. Screening the different designs with various antibody binding and cellular assays revealed that combining a branched design with the addition of lipid moieties greatly enhanced the immunoreactivity

A combined nucleocapsid vaccine induces vigorous SARS-CD8+ T-cell immune responses

Several studies have shown that cell-mediated immune responses play a crucial role in controlling viral replication. As such, a candidate SARS vaccine should elicit broad CD8+ T-cell immune responses. Several groups of mice were immunized alone or in combination with SARS-nucleocapsid immunogen. A high level of specific SARS-CD8+ T-cell response was demonstrated in mice that received DNA encoding the SARS-nucleocapsid, protein and XIAP as an adjuvant. We also observed that co-administration of a plasmid expressing nucleocapsid, recombinant protein and montanide/CpG induces high antibody titers in immunized mice. Moreover, this vaccine approach merits further investigation as a potential candidate vaccine against SARS

Enhancing Oral Vaccine Potency by Targeting Intestinal M Cells

The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M) cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells

Virological and Immunological Aspects of AIDS Pathogenesis

The most common and serious problem associated with long term antiretroviral therapy is waning efficacy over time. To date. a number of studies has suggested an association between drug resistance and clinical deterioration. However. a precise causal relationship has yet to be demonstrated. In a large American clinical trial. resistance to zidovudine (ZDV) was predictive of subsequent disease progression if this therapy was continued. Surprisingly. this was also predictive of deterioration if therapy was changed to didanosine (ddl). This suggests that other factors (perhaps virological and immunological) which may be present in addition to resistance. were as important (if not more so) in predicting clinical outcomes. It is likely that viral load. resistance. viral phenotype and alterations in immune function interact in this regard. Proper· studies may allow us to determine a “threshold” for a composite virological and immunological parameter beyond which disease progression will occur. As more antiretroviral agents become available. we will be in a position to intervene to “improve” laboratory markers and monitor them prospectively. potentially to maintain clinical latency for an indefinite period of time. In the authors' laboratories, a quantitative polymerase chain reaction assay for the evaluation of circulating proviral load has been developed. In an initial study of 70 patients. proviral load/ 106 CD4 cells was clearly associated with the severity of immune disease. with up to 9.6% of cells being infected in subjects with CD4 cell counts below 200/µL. However. large variability in proviral load among individuals with comparable or dissimilar CD4 cell counts precludes the use of this measurement as an individual marker of the severity of immune disease. More recent work evaluated the combined use of proviral load (expressed as a dichotomous variable based on values above or below one copy/a03 CD4 cells) and resistance in a prospective fashion. In five patients with high proviral loads and isolates resistant to their current therapy. a mean decrease of 72 CD4 cells/µL was observed over 12 months of observation. In contrast. in six patients with low proviral loads and sensitive isolates. there was a mean increase of 43 CD4 cells/µL. It appears that virological markers are associated with immune disease progression in this small cohort of patients. The association appears most marked when the two virological parameters are considered together rather than individually. The association is not always a tight one. and this may relate to a number of unmeasured factors. including viral phenotype. plasma viremia. and the immune response to HIV infection. Additional work incorporating these parameters into analysis is currently underway in the authors’ centre

Reactogenicity to a live attenuated varicella vaccine in Canadian children

OBJECTIVE: To assess the reactogenicity and safety of a thermostable, high titre, varicella vaccine in healthy infants and children

Three-year follow-up of protection rates in children given varicella vaccine

OBJECTIVE: To determine the rate and severity of subsequent varicella and zoster among children given a varicella vaccine