Procedia in vaccinology最新文献

Background

In Japan, a number of people who die from influenza are still increasing however seasonal influenza immunization rates among children are still low and estimated to be around 30%. Given these circumstance we organized questionnaire surveys from 2009 to 2010 to examine the factors influencing awareness of mothers under frame work of Health Belief Model (HBM) that affect seasonal flu immunization acceptance among children.

Method

From 2009 to 2010, we sent questionnaires to randomly selected university graduated women. The questionnaire asked their age, seasonal flu immunization status of their children, working status, subjective life standards, regions where they live, perceived severity of flu to their children, perceived susceptibility to flu of their children, perceived efficacy or non-efficacy of flu vaccination on their children, barriers to vaccination such that flu vaccination is non-mandatory, fear for side effect, busy and others, cues to the action such as family doctors recommendations and willing to pay (WTP). After the correlation of each variable was tested by spearman test (SPSS 17.0) adjusted logistic regression analysis predicting routine vaccination was done. Results; we sent 554 questionnaires to women and 226 mothers (Age 44.67±5.09) responded and 220 responses were analyzed. Among children of respondents, 41.2% were routinely flu shot vaccinated. From the multivariate logistic regression model, HBM framework showed that perceived susceptibility to flu of their children's (aOR=1.46, p>0.05), perceived severity of flu (aOR=1.14, p>0.05) to their children, perceived non-efficacy of flu vaccination on their children (aOR=0.12, p<0.01), and cue to the action such as family doctors’ recommendations (aOR=2.47, p<0.01) and knowing of the flu vaccination subsidy (aOR=1.96, p>0.05) were positive factors for flu immunization acceptance. On contrary, barriers such as subjective lower life standard (aOR=0.59, p<0.05), flu-shot was not mandatory (aOR=0.15, p<0.01), fear from side effects (aOR=0.31, p<0.05) and number of children (aOR=0.64, p<0.05) were negative factors. Discussion; Correct education and knowledge dissemination for mothers are necessary to raise the low coverage rate of their children in order to prepare potential future flu pandemic.

Hypervaccination against infectious diseases is a radically new efficient strategy of preventive vaccination. Its objective is specific abrogation of innate susceptibility of the organism to the disease achieved by blockage of the pathogen specific binding sites (receptors) on the surface of target cells by the anti-receptors of the vaccine. The new strategy is based on competition between the anti-receptors of the vaccine and those of the pathogen for the receptors on target cells. The mechanism of hypervaccination is a rapid maximal saturation of the target cells receptors with a massive dose of anti-receptors contained in a live or inactivated vaccine. Protection of the naturally susceptible organism against infection initially occurs by the mechanism of homologous interference at the stage of the pathogen's binding to the target cell rather than by reactions of adaptive immunity. At a later stage, early protection is followed by a long-term intense immune response with a marked seroconversion. Thus, a high dose vaccination confers protection in two stages, interference at the receptor binding level and immune response. Administering a safe vaccine with a high content of anti-receptors protects naturally susceptible animals against disease and death at challenge 12-72 hrs after vaccination with no chronic infection establishing. An apparent resistance of the organism against a severe challenge soon after vaccination is likely to be due to a full or virtually full saturation of the target cells receptors with the vaccine anti-receptors. The efficiency of prompt protection in field conditions has first been shown in the eradication of classical swine fever (CSF) in two countries, Russia and Belarus.

The reduced immunogenicity and effectiveness of influenza vaccines in subjects presenting high risk of influenza-related complications, hospitalization and death, led the innovative drive to search for new strategies to implement the immune response elicited by influenza vaccines including addition of adjuvants, and use of alternative routes of antigen delivery.In this study we evaluated and compared the immune antibody response induced in 252 elderly volunteers living in nursing homes after immunization with three different 2012-2013 seasonal trivalent inactivated influenza vaccines: a conventional split vaccine (n=26), and two potentiated vaccines (a subunit vaccine adjuvanted with MF59 (n=137) or a split vaccine administered intradermally (n=89)), specially licensed for elderly people. Haemagglutination inhibiting (HI) antibody titers were assessed in blood samples collected before and one month after vaccination.The results were evaluated as increase in HI titers found comparing pre- and post-vaccination sera and according to the Committee for Medicinal Products for Human Use (CHMP) criteria for approval of influenza vaccines in the elderly. Significant antibody increases and fulfillment of all the three CHMP requirements were observed against A/H3N2 and B antigens following immunization with the two potentiated vaccines. After immunization with conventional vaccine responses were lower against A/H3N2 and equivalent against the B antigen. The two potentiated vaccines induced significant antibody increases against A/H1N1 antigen, however, only one of the CHMP criteria was reached. The HI antibody increases after conventional vaccine were significant only for the geometric mean titer and none of the CHMP criteria was fulfilled. The antibody responses induced by the two potentiated vaccines against the three vaccine antigens wereequivalent although post-vaccination titers against the B antigen tended to be higher in subjects vaccinated with intradermal vaccine than in individuals receiving MF59-adjuvanted vaccine.

In conclusion the use of MF59 adjuvant and intradermal vaccination appear to be appropriate strategies to address the challenge of declining immune response in the elderly after influenza vaccination.

Progressin development of tuberculosis (TB) vaccines largely depends on the availability of animal models to test their safety and efficacy before starting with expensive clinical trials. The present study provides a comprehensive evaluation of bacillus Calmette-Guerin (BCG) effects on clinical, immunological, pathological and bacteriological parameters in goats after an experimental challenge with Mycobacterium caprae.Vaccination of goats with BCG reduced the volume of lung gross lesions, the bacterial load in pulmonary lymph nodes and increased the weight gain when compared to unvaccinated animals. Differences in post-challenge IFN-γ responses to ESAT-6/CFP-10 were found to be a useful follow-up biomarker of disease progression and vaccine efficacy. Our results endorse this animal model for further TB vaccine trials.

Visceral leishmaniasis is a chronicand lethal parasite disease against which no human vaccine is available.Hepato- splenomegaly and a progressive suppression of the cellular immune response are among its most important clinical signs. The characteristic cellular immunosupression was described as being mediated in part, through the spatial segregation of dendritic cells (DCs) and T cell lymphocytes due to altered frequencies and migration capabilities of DCs. In this investigation, we measured the spleen/body relative weight, the spleen parasite load and the total counts of spleen DCs of C57BL6 mice infected with Leishmania chagasi. All the variables achieved their maximum at 30 days after infection. We detected in infected animals a 5.08 fold increase of spleen relative weight, a 19.6 fold increase of parasite load and a 4.55 increase of total DCs counts, when compared to naïve controls. We further analysed the efficacy of the NH36 and F3 vaccines formulated in saponin in prevention of visceral leishmaniasis. When compared to the infected controls, both vaccines determined strong protection. The F3 vaccine induced the highest efficacy showing 95% and 49% reduction the parasite load and splenomegaly, respectively. The NH36 vaccine, on the other hand, developed a slightly lower but still significant protection reducing by 87% the parasite load and by 39% the spleen relative weight. Both vaccines also prevented the increase in total counts of DCs with no significant difference between them (36% by the NH36 and 26% by the F3 vaccine). Our results suggest that vaccination against murine visceral leishmaniasis with the NH36 vaccine can prevent the development of the disease by preventing the DCs dysfunction-related immunosupression. Additionally, they disclose the potential use of the NH36 C-terminal moiety, the F3 peptide for optimization of the vaccine efficacy.

Nanoparticles (NPs) have great potential as advanced delivery systems for cancer immunotherapy. PEGylated-Poly- lactide-co-glycolic acid-based (PLGA-PEG) NPs were prepared by double-emulsion solvent evaporation technique, using ovalbumin (OVA) as a model antigen. Glycol Chitosan and block co-polymer Pluronic F127 were used in order to best attain the most efficient parameters for cancer immunotherapy. OVA-loaded PLGA-PEG NPs presented a narrow size distribution with an average size of 167 nm witha polidisperity index (PdI)0.167 and zeta potential values close to neutrality (-1.66 mV), which is desired for a particulate cancer vaccine to overcome their premature capture by macrophages. The encapsulation efficiency (EE) and loading capacity (LC) of these NPs were 57.5% and 29 μg/mg, respectively. PLGA-PEG NPs modified with Pluronic F127 presented slightly higher Z- Average (180 nm with a PdI 0.18), and ZP (ZP -1.78 mV), but lower EE and LC (32% and 16 μg/mg). The effect of NPs on dendritic cell viabilitywas evaluated using Alamar Blue® assays.

Attenuated Yersinia pestis strain EV NIIEG is a licensed live plague vaccine (LPV) for human use in Russia that can elicit protection against both the bubonic and pneumonic forms of disease. However, little is known about the mechanisms underlying the formation of immunity to Y. pestis provided by this vaccine. Our recent study reported a prevalence of specific IgG antibodies to the capsular antigen F1 and the type three secretion system (T3SS) structural subunit YscF in humans immunized with live plague vaccine. In this study, IgG subclasses of antibodies to the plague antigens F1 and YscF in the sera of vaccinees were determined by using an enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies. IgG subclass antibodies to F1 antigen were predominantly IgG1, although IgG2 and IgG4 subclasses were detectable. The IgG1 titers were markedly higher in donors who received multiple annual injections, while the IgG2 and IgG4 titers showed no increase and stayed low in all donors. The IgG1 anti-F1 remained detectable even 20 years post-vaccination, suggesting a long-term immunity. Sera of YscF-positive donors also contained predominantly IgG1-specific antibodies. The IgG2 and IgG4 titers to YscF were undetectable in all donors, including those who received multiple vaccinations. In conclusion, we describe for the first time that IgG1 is a dominating isotype for both F1 and YscF antigens in humans immunized with live plague vaccine.

Live plague vaccine (LPV) was widely used to control Yersinia pestis infection in the middle of 20^th century, and this vaccine still remains a choice for prophylaxis of plague. Nevertheless, human immunity to LPV was poorly investigated, and was limited mostly to examining the antibody response to the capsular antigen F1 and lipopolysaccharide of Y. pestis. In this work we tested sera from 19 individuals who received multiple immunizations with attenuated strain of Y. pestis EV NIIEG that is employed as a LPV in Russia. Sera from 15 healthy donors, which had no contact with Y. pestis or LPV were used as a control. All sera were studied for the presence of antigen-specific antibodies in immunoblot and to a panel of highly purified recombinant Y. pestis proteins. We found that donors vaccinated with EV NIIEG contained antibodies to one or a few antigens, such as YopM, LcrV, Pla, and F1, in the range of 31.6- 78.9%. However, sera of some non-vaccinated donors reacted positively with at least one of these antigens. Similar cross-reactivity was observed earlier during testing of F1/LcrV subunit vaccine in humans and non-human primates. In contrast, our study revealed that human humoral immune response to YscF was highly specific. Antibodies to this antigen were detected in sera of 10 out of 19 vaccinees, while all 15 control sera from non-vaccinated donors were negative. YscF represents a subunit of the translocation needle of the type 3 secretion system (T3SS) of Yersinia, and forms a polymeric structure. Apparently, successful human vaccination with LPV leads to the assembly of T3SS apparatus in vivo. Thus, we showed for the first time that YscF can be considered as a highly specific marker of evaluation of human immune response to live plague vaccine.