CHARACTERISATION OF THE HUMAN ANTIBODY RESPONSE TO THE UK ANTHRAX VACCINE

Triose phosphate isomerase from the blood fluke Schistosoma mansoni:Biochemical characterisation of a potential drug and vaccine target

The glycolytic enzyme triose phosphate isomerase from Schistosoma mansoni is a potential target for drugs and vaccines. Molecular modelling of the enzyme predicted that a Ser-Ala-Asp motif which is believed to be a helminth-specific epitope is exposed. The enzyme is dimeric (as judged by gel filtration and cross-linking), resistant to proteolysis and highly stable to thermal denaturation (melting temperature of 82.0°C). The steady-state kinetic parameters are high (Km for dihydroxyacetone phosphate is 0.51mM; Km for glyceraldehyde 3-phosphate is 1.1mM; kcat for dihydroxyacetone phosphate is 7800s(-1) and kcat for glyceraldehyde 3-phosphate is 6.9s(-1)).

The marginal willingness-to-pay for attributes of a hypothetical HIV vaccine

This paper estimates the marginal willingness-to-pay for attributes of a hypothetical HIV vaccine using discrete choice modeling. We use primary data from 326 respondents from Bangkok and Chiang Mai, Thailand, in 2008–2009, selected using purposive, venue-based sampling across two strata. Participants completed a structured questionnaire and full rank discrete choice modeling task administered using computer-assisted personal interviewing. The choice experiment was used to rank eight hypothetical HIV vaccine scenarios, with each scenario comprising seven attributes (including cost) each of which had two levels. The data were analyzed in two alternative specifications: (1) best-worst; and (2) full-rank, using logit likelihood functions estimated with custom routines in Gauss matrix programming language. In the full-rank specification, all vaccine attributes are significant predictors of probability of vaccine choice. The biomedical attributes of the hypothetical HIV vaccine (efficacy, absence of VISP, absence of side effects, and duration of effect) are the most important attributes for HIV vaccine choice. On average respondents are more than twice as likely to accept a vaccine with 99% efficacy, than a vaccine with 50% efficacy. This translates to a willingness to pay US$383 more for a high efficacy vaccine compared with the low efficacy vaccine. Knowledge of the relative importance of determinants of HIV vaccine acceptability is important to ensure the success of future vaccination programs. Future acceptability studies of hypothetical HIV vaccines should use more finely grained biomedical attributes, and could also improve the external validity of results by including more levels of the cost attribute.

Measurements of immune responses for establishing correlates of vaccine protection against HIV

Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of protection, both for ongoing and future HIV-1 vaccine candidates; specific efforts were made to engage young scientists. We discuss here the highlights from the meeting regarding the progress made and the way forward for a protective HIV-1 vaccine.

Identification of systemic immune response markers through metabolomic profiling of plasma from calves given an intra-nasally delivered respiratory vaccine

Vaccination procedures within the cattle industry are important disease control tools to minimize economic and welfare burdens associated with respiratory pathogens. However, new vaccine, antigen and carrier technologies are required to combat emerging viral strains and enhance the efficacy of respiratory vaccines, particularly at the point of pathogen entry. New technologies, specifically metabolomic profiling, could be applied to identify metabolite immune-correlates representative of immune protection following vaccination aiding in the design and screening of vaccine candidates. This study for the first time demonstrates the ability of untargeted UPLC-MS metabolomic profiling to identify metabolite immune correlates characteristic of immune responses following mucosal vaccination in calves. Male Holstein Friesian calves were vaccinated with Pfizer Rispoval® PI3 + RSV intranasal vaccine and metabolomic profiling of post-vaccination plasma revealed 12 metabolites whose peak intensities differed significantly from controls. Plasma levels of glycocholic acid, N-[(3α,5β,12α)-3,12-Dihydroxy-7,24-dioxocholan-24-yl]glycine, uric acid and biliverdin were found to be significantly elevated in vaccinated animals following secondary vaccine administration, whereas hippuric acid significantly decreased. In contrast, significant upregulation of taurodeoxycholic acid and propionylcarnitine levels were confined to primary vaccine administration. Assessment of such metabolite markers may provide greater information on the immune pathways stimulated from vaccine formulations and benchmarking early metabolomic responses to highly immunogenic vaccine formulations could provide a means for rapidly assessing new vaccine formulations. Furthermore, the identification of metabolic systemic immune response markers which relate to specific cell signaling pathways of the immune system could allow for targeted vaccine design to stimulate key pathways which can be assessed at the metabolic level.

Fasciola hepatica vaccine: We may not be there yet but we're on the right road

Major advances have been made in identifying potential vaccine molecules for the control of fasciolosis in livestock but we have yet to reach the level of efficacy required for commercialisation. The pathogenesis of fasciolosis is associated with liver damage that is inflicted by migrating and feeding immature flukes as well as host inflammatory immune responses to parasite-secreted molecules and tissue damage alarm signals. Immune suppression/modulation by the parasites prevents the development of protective immune responses as evidenced by the lack of immunity observed in naturally and experimentally infected animals. In our opinion, future efforts need to focus on understanding how parasites invade and penetrate the tissues of their hosts and how they potentiate and control the ensuing immune responses, particularly in the first days of infection. Emerging 'omics' data employed in an unbiased approach are helping us understand liver fluke biology and, in parallel with new immunological data, to identify molecules that are essential to parasite development and accessible to vaccine-induced immune responses.

The role of microneedles for drug and vaccine delivery

INTRODUCTION: Transdermal drug delivery offers a number of advantages for the patient, not only due to its non-invasive and convenient nature, but also due to factors such as avoidance of first-pass metabolism and prevention of gastrointestinal degradation. It has been demonstrated that microneedles (MNs) can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum, and creating a pathway for drug permeation to the dermal tissue below.

AREAS COVERED: MNs have been extensively investigated for drug and vaccine delivery. The different types of MN arrays and their delivery capabilities are discussed in terms of drugs, including biopharmaceutics and vaccines. Patient usage and effects on the skin are also considered.

EXPERT OPINION: MN research and development is now at the stage where commercialisation is a viable possibility. There are a number of long-term safety questions relating to patient usage which will need to be addressed moving forward. Regulatory guidance is awaited to direct the scale-up of the manufacturing process alongside provision of clearer patient instruction for safe and effective use of MN devices.