HPV vaccine acceptance in males

Background Despite Human Papillomavirus (HPV)’s impact on the health of both sexes, there is debate around the inclusion of males in HPV vaccination programmes. The aim of this scoping review was to synthesize the evidence on vaccine acceptability to males. Given that the vaccine is most effective in adolescent males, vaccine acceptance in parents and health care professionals (HCPs) was also examined. Method A rapid synthesis using specified key words of published systematic reviews into vaccine acceptability in adolescent males, parents and HCPs was conducted. The most common electronic databases were searched including: Medline, EMBASE, PsychINFO, and CINAHL. Results There was variability amongst studies with respect to design and methodological approaches. Despite this there appears to be a positive attitude towards male HPV vaccination from both parents and older males. There is currently insufficient evidence on vaccine acceptance to adolescent males. Understanding the risks involved in HPV acquisition, and receiving a recommendation from a HCP, appear to be the major factors involved in males deciding to be vaccinated. Parents consistently report the importance of a HCP recommendation, yet HCPs (in the US) appear to have a preference for vaccinating older than younger adolescents, and for vaccinating females. Conclusions The absence of an agreed definition of vaccine acceptance leads to a lack of a universally accepted tool for its measurement. This makes comparison of studies difficult. With no established theoretical framework the identification and exploration of factors that influence vaccine uptake can be variable. In addition, acceptance is not indicative of uptake. The majority of studies are cross-sectional which makes the identification of factors that lead to actual vaccine uptake difficult. Prospective, longitudinal studies identifying individuals that acted on vaccine intention should be conducted to identify the factors that mediate the uptake.

Immunological and histological changes of gilthead sea bream (Sparus Aurata) to Alum, when used as an adjuvnat in Photobacterium damselae ssp piscicida vaccine

Dissertação mest., Aquacultura e Pescas, Universidade do Algarve, 2006

Development of a melanoma therapeutic vaccine candidate by the coencapsulation of melanoma antigen peptides and toll-like receptor ligands as adjuvants into polymeric nanoparticles

Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2014

Lyophilisation of influenza, rabies and Marburg lentiviral pseudotype viruses for the development and distribution of a neutralisation-assay based diagnostic kit

Pseudotype viruses (PVs) are chimeric, replication-deficient virions that mimic wild-type virus entry mechanisms and can be safely employed in neutralisation assays, bypassing the need for high biosafety requirements and performing comparably to established serological assays. However, PV supernatant necessitates -80°C long-term storage and cold-chain maintenance during transport, which limits the scope of dissemination and application throughout resource-limited laboratories. We therefore investigated the effects of lyophilisation on influenza, rabies and Marburg PV stability, with a view to developing a pseudotype virus neutralisation assay (PVNA) based kit suitable for affordable global distribution. Infectivity of each PV was calculated after lyophilisation and immediate reconstitution, as well as subsequent to incubation of freeze-dried pellets at varying temperatures, humidities and timepoints. Integrity of glycoprotein structure following treatment was also assessed by employing lyophilised PVs in downstream PVNAs. In the presence of 0.5M sucrose-PBS cryoprotectant, each freeze-dried pseudotype was stably stored for 4 weeks at up to 37°C and could be neutralised to the same potency as unlyophilised PVs when employed in PVNAs. These results confirm the viability of a freeze-dried PVNA-based kit, which could significantly facilitate low-cost serology for a wide portfolio of emerging infectious viruses.

Massive shift in the pneumococcal nasopharyngeal flora after the 7-valent conjugate vaccine: epidemiological studies and testing pathogenic potential in animal models

Dissertation presented to obtain the PhD degree in Biology/Molecular Biology by Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica

Influenza surveillance using data from a telemedicine centre.

OBJECTIVES: This study aimed at investigating whether data from medical teleconsultations may contribute to influenza surveillance. METHODS: International Classification of Primary Care 2nd Edition (ICPC-2) codes were used to analyse the proportion of teleconsultations due to influenza-related symptoms. Results were compared with the weekly Swiss Sentinel reports. RESULTS: When using the ICPC-2 code for fever we could reproduce the seasonal influenza peaks of the winter seasons 07/08, 08/09 and 09/10 as depicted by the Sentinel data. For the pandemic influenza 09/10, we detected a much higher first peak in summer 2009 which correlated with a potential underreporting in the Sentinel system. CONCLUSIONS: ICPC-2 data from medical teleconsultations allows influenza surveillance in real time and correlates very well with the Swiss Sentinel system.

Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine in HIV-infected adults on combination antiretroviral therapy: a phase I/II, randomized trial.

OBJECTIVE: Tuberculosis (TB) is highly prevalent among HIV-infected people, including those receiving combination antiretroviral therapy (cART), necessitating a well tolerated and efficacious TB vaccine for these populations. We evaluated the safety and immunogenicity of the candidate TB vaccine M72/AS01 in adults with well controlled HIV infection on cART. DESIGN: A randomized, observer-blind, controlled trial (NCT00707967). METHODS: HIV-infected adults on cART in Switzerland were randomized 3 : 1 : 1 to receive two doses, 1 month apart, of M72/AS01, AS01 or 0.9% physiological saline (N = 22, N = 8 and N = 7, respectively) and were followed up to 6 months postdose 2 (D210). Individuals with CD4⁺ cell counts below 200 cells/μl were excluded. Adverse events (AEs) including HIV-specific and laboratory safety parameters were recorded. Cell-mediated (ICS) and humoral (ELISA) responses were evaluated before vaccination, 1 month after each dose (D30, D60) and D210. RESULTS: Thirty-seven individuals [interquartile range (IQR) CD4⁺ cell counts at screening: 438-872 cells/μl; undetectable HIV-1 viremia] were enrolled; 73% of individuals reported previous BCG vaccination, 97.3% tested negative for the QuantiFERON-TB assay. For M72/AS01 recipients, no vaccine-related serious AEs or cART-regimen adjustments were recorded, and there were no clinically relevant effects on laboratory safety parameters, HIV-1 viral loads or CD4⁺ cell counts. M72/AS01 was immunogenic, inducing persistent and polyfunctional M72-specific CD4⁺ T-cell responses [medians 0.70% (IQR 0.37-1.07) at D60] and 0.42% (0.24-0.61) at D210, predominantly CD40L⁺IL-2⁺TNF-α⁺, CD40L⁺IL-2⁺ and CD40L⁺IL-2⁺TNF-α⁺IFN-γ⁺]. All M72/AS01 vaccines were seropositive for anti-M72 IgG after second vaccination until study end. CONCLUSION: M72/AS01 was clinically well tolerated and immunogenic in this population, supporting further clinical evaluation in HIV-infected individuals in TB-endemic settings.

Harmonization guidelines for HLA-peptide multimer assays derived from results of a large scale international proficiency panel of the Cancer Vaccine Consortium.

PURPOSE: The Cancer Vaccine Consortium of the Cancer Research Institute (CVC-CRI) conducted a multicenter HLA-peptide multimer proficiency panel (MPP) with a group of 27 laboratories to assess the performance of the assay. EXPERIMENTAL DESIGN: Participants used commercially available HLA-peptide multimers and a well characterized common source of peripheral blood mononuclear cells (PBMC). The frequency of CD8+ T cells specific for two HLA-A2-restricted model antigens was measured by flow cytometry. The panel design allowed for participants to use their preferred staining reagents and locally established protocols for both cell labeling, data acquisition and analysis. RESULTS: We observed significant differences in both the performance characteristics of the assay and the reported frequencies of specific T cells across laboratories. These results emphasize the need to identify the critical variables important for the observed variability to allow for harmonization of the technique across institutions. CONCLUSIONS: Three key recommendations emerged that would likely reduce assay variability and thus move toward harmonizing of this assay. (1) Use of more than two colors for the staining (2) collect at least 100,000 CD8 T cells, and (3) use of a background control sample to appropriately set the analytical gates. We also provide more insight into the limitations of the assay and identified additional protocol steps that potentially impact the quality of data generated and therefore should serve as primary targets for systematic analysis in future panels. Finally, we propose initial guidelines for harmonizing assay performance which include the introduction of standard operating protocols to allow for adequate training of technical staff and auditing of test analysis procedures.

Immune monitoring design within the developmental pipeline for an immunotherapeutic or preventive vaccine

Immunotherapy is defined as the treatment of disease by inducing, enhancing, or suppressing an immune response, whereas preventive vaccination is intended to prevent the development of diseases in healthy subjects. Most successful prophylactic vaccines rely on the induction of high titers of neutralizing antibodies. It is generally thought that therapeutic vaccination requires induction of robust T-cell mediated immunity. The diverse array of potential or already in use immunotherapeutic and preventive agents all share the commonality of stimulating the immune system. Hence, measuring those vaccination-induced immune responses gives the earliest indication of vaccine take and its immune modulating effects.

Malaria vaccine candidate: design of a multivalent subunit α-helical coiled coil poly-epitope.

A new strategy for the rapid identification of new malaria antigens based on protein structural motifs was previously described. We identified and evaluated the malaria vaccine potential of fragments of several malaria antigens containing α-helical coiled coil protein motifs. By taking advantage of the relatively short size of these structural fragments, we constructed different poly-epitopes in which 3 or 4 of these segments were joined together via a non-immunogenic linker. Only peptides that are targets of human antibodies with anti-parasite in vitro biological activities were incorporated. One of the constructs, P181, was well recognized by sera and peripheral blood mononuclear cells (PBMC) of adults living in malaria-endemic areas. Affinity purified antigen-specific human antibodies and sera from P181-immunized mice recognised native proteins on malaria-infected erythrocytes in both immunofluorescence and western blot assays. In addition, specific antibodies inhibited parasite development in an antibody dependent cellular inhibition (ADCI) assay. Naturally induced antigen-specific human antibodies were at high titers and associated with clinical protection from malaria in longitudinal follow-up studies in Senegal.

New generation vaccine induces effective melanoma-specific CD8+ T cells in the circulation but not in the tumor site.

Although increasing evidence suggests that CTL are important to fight the development of some cancers, the frequency of detectable tumor-specific T cells is low in cancer patients, and these cells have generally poor functional capacities, compared with virus-specific CD8(+) T cells. The generation with a vaccine of potent CTL responses against tumor Ags therefore remains a major challenge. In the present study, ex vivo analyses of Melan-A-specific CD8(+) T cells following vaccination with Melan-A peptide and CpG oligodeoxynucleotides revealed the successful induction in the circulation of effective melanoma-specific T cells, i.e., with phenotypic and functional characteristics similar to those of CTL specific for immunodominant viral Ags. Nonetheless, the eventual impact on tumor development in vaccinated melanoma donors remained limited. The comprehensive study of vaccinated patient metastasis shows that vaccine-driven tumor-infiltrating lymphocytes, although activated, still differed in functional capacities compared with blood counterparts. This coincided with a significant increase of FoxP3(+) regulatory T cell activity within the tumor. The consistent induction of effective tumor-specific CD8(+) T cells in the circulation with a vaccine represents a major achievement; however, clinical benefit may not be achieved unless the tumor environment can be altered to enable CD8(+) T cell efficacy.

How critical is timing for the diagnosis of influenza in general practice?

QUESTIONS UNDER STUDY: The diagnostic significance of clinical symptoms/signs of influenza has mainly been assessed in the context of controlled studies with stringent inclusion criteria. There was a need to extend the evaluation of these predictors not only in the context of general practice but also according to the duration of symptoms and to the dynamics of the epidemic. PRINCIPLES: A prospective study conducted in the Medical Outpatient Clinic in the winter season 1999-2000. Patients with influenza-like syndrome were included, as long as the primary care physician envisaged the diagnosis of influenza. The physician administered a questionnaire, a throat swab was performed and a culture acquired to document the diagnosis of influenza. RESULTS: 201 patients were included in the study. 52% were culture positive for influenza. By univariate analysis, temperature >37.8 degrees C (OR 4.2; 95% CI 2.3-7.7), duration of symptoms <48 hours (OR 3.2; 1.8-5.7), cough (OR 3.2; 1-10.4) and myalgia (OR 2.8; 1.0-7.5) were associated with a diagnosis of influenza. In a multivariable logistic analysis, the best model predicting influenza was the association of a duration of symptom <48 hours, medical attendance at the beginning of the epidemic (weeks 49-50), fever >37.8 and cough, with a sensitivity of 79%, specificity of 69%, positive predictive value of 67%, negative predictive value of 73% and an area under the ROC curve of 0.74. CONCLUSIONS: Besides relevant symptoms and signs, the physician should also consider the duration of symptoms and the epidemiological context (start, peak or end of the epidemic) in his appraisal, since both parameters considerably modify the value of the clinical predictors when assessing the probability of a patient having influenza.