High level of exposure to hepatitis B virus infection in a vulnerable population of a low endemic area: A challenge for vaccination coverage.

OBJECTIVES: To evaluate the epidemiological and molecular features of HBV infection among recyclable waste collectors. METHODS: The participants were recruited from the dumping ground and recycling cooperatives in Campo Grande, Brazil, and were screened for hepatitis B and C, and HIV serological markers by ELISA, confirmed by PCR. RESULTS: Among 278 participants, 63.7% (95% CI: 58.0-69.3) were considered susceptible to HBV infection. The prevalence rate of HBV exposure was 10.1% (95% CI: 6.5-13.6) and 0.4% (95% CI: 0.1-0.6) were chronic carriers. Age ≥45 years (AOR=7.15), history of homosexual contact (AOR=5.29), tattoo (AOR=4.92) and history of surgery (AOR=2.89) were factors associated with ever infection. Age 18-25 years (AOR=4.63), educational level ≥9 years (AOR=1.98) and knowledge about HBV transmission (AOR=3.08) were associated with serological HBV vaccination like profile (26.2%; 95% CI: 21.1-31.4). CONCLUSIONS: Despite the availability and efficacy of HBV vaccine, this study found high HBV exposure and proportion of susceptible adults in a low endemic area. Vaccination and screening campaigns using accessible language to the economically disadvantaged populations can reduce the number of people susceptible to HBV infection.

Vanadium pentoxide inhalation provokes germinal center hyperplasia and suppressed humoral immune responses.

Vanadium, an important air pollutant derived from fuel product combustion, aggravates respiratory diseases and impairs cardiovascular function. In contrast, its effects on immune response are conflicting. The aim of our work was to determine if spleens of vanadium-exposed CD1 mice showed histological lesions that might result in immune response malfunction. One hundred and twelve CD-1 male mice were placed in an acrylic box and inhaled 0.02 M vanadium pentoxide (V2O5); actual concentration in chamber approximately 1.4 mg V2O5/m(3)) for 1 hr/d, twice a week, for 12 wk. Control mice inhaled only vehicle. Eight mice were sacrificed prior to the exposures. Eight control and eight V2O5-exposed mice were sacrificed 24 hr after the second exposure of each week until the 12-wk study was over. Another 8 mice that completed the 12-wk regimen were immunized with recombinant Hepatitis B surface antigen (HBsAg; three times over an 8-wk period) before sacrifice and analyses of their levels of anti-HBsAg antibody (HBSAb) using ELISA. In all studies, at sacrifice, blood samples were obtained by direct heart puncture and the spleen was removed, weighed and processed for H-E staining and quantitation of CD19 cells. The results indicated that the spleen weight of V2O5-exposed animals peaked at 9 wk (546 +/- 45 vs. 274 +/- 27 mg, p < 0.0001) and thereafter progressively decreased (321 +/- 39 mg at 12 wk, p < 0.001; control spleen = 298 +/- 35 mg). Spleens of V2O5-exposed animals showed an increased number of very large and non-clearly delimited germinal centers (that contained more lymphocytes and megakaryocytes) compared to those of control mice. In addition, their red pulp was poorly delimited and had an increase in CD19+ cells within hyperplasic germinal nodes. The mean HBsAb levels in immunized control mice were greater than that in the exposed hosts (i.e., OD = 0.39 +/- 0.03 vs. 0.11 +/- 0.05, p < 0.01). HBsAb avidity dropped to a value of 40 in V2O5-exposed animals vs. 86 in controls (p < 0.0001). We conclude that the chronic inhalation of V2O5, a frequent particle (PM(2.5)) component, induces histological changes and functional damage to the spleen, each of which appear to result in severe effects on the humoral immune response.

Comparative study of the immunogenicity and immunoenhancing effects of two hepatitis B core antigen variants in mice by nasal administration.

The hepatitis B virus (HBV) core antigen (HBcAg) is a potent immunogen in animal models and humans and has been used as a carrier for several antigens; however, the mucosal immunogenicity of HBcAg has been poorly studied. In this study, we explored the immunogenicity and the immunoenhancing effect elicited by two different variants of the recombinant complete nucleocapside of HBV in mice by intranasal route. For this purpose, we used as co-administered antigen, the HBV surface protein (HBsAg) and the antibody response in sera was evaluated after each dose. To analyze the specificity of the generated antibody response, the recognition of lineal epitopes was evaluated on a cellulose membrane bearing 12 mer peptides covering the HBcAg sequence. The obtained results evidenced that the intranasal immunogenicity of both variants of HBcAg was similar and high, developing early responses of IgG. The immunoenhancing effect on the HBsAg-specific antibody response was also similar for both variants. The results of the recognition of lineal epitopes study evidenced a similar recognition pattern to all sera and vaginal lavages samples generated by the immunization of mice with the two variants of HBcAg, and also similar to a pool of human anti-HBcAg positive sera samples.

Coinoculation with hepatitis B surface and core antigen promotes a Th1 immune response to a multiepitopic protein of HIV-1.

It has been defined that strong and multispecific cellular immune responses correlate with a better prognosis during the course of chronic diseases. A cross-enhancing effect on the resulting immune response obtained by the coadministration of recombinant hepatitis B virus (HBV) surface and core Ag was recently observed. With the objective of studying the effect of such Ag on the immune response to coinoculated heterologous Ag and vice versa, several formulations containing the recombinant HBV Ag and a multiepitopic protein (CR3) composed by CTL and Th epitopes from HIV-1 were evaluated by s.c. and mucosal administration. Combinations of two and three Ag were evaluated for cellular and humoral immune responses. The results showed that the best Ag combination for nasal immunization was the mixture comprising the CR3 recombinant HIV protein and both HBV Ag. Similarly, it was also the best formulation for s.c. immunization in aluminium phosphate adjuvant. In conclusion, it is possible to induce a Th1 stimulation of the cellular immune response specific for a HIV-based recombinant protein by formulating this Ag with the recombinant HBV Ag.

Influence of aluminum-based adjuvant on the immune response to multiantigenic formulation.

Several adjuvants have been described and tested in humans. However, the aluminum-based adjuvants remain the most widely used component in vaccines today. Emerging data suggest that aluminum phosphate and aluminum hydroxide adjuvants do not promote a strong commitment to the helper T cell type 2 (Th2) pathway when they are coadministered with some Th1 adjuvants. In this regard, subtle differences between both aluminum-based adjuvants have been demonstrated. We have previously shown that subcutaneous immunization, in aluminum phosphate, of a mixture comprising the surface and core antigens of hepatitis B virus (HBV) and the multiepitopic protein CR3 of human immunodeficiency virus type 1 elicits a CR3-specific Th1 immune response. In these experiments, the antigens were adjuvated at the same time. As the final selection of the best adjuvant should be based on experimental evidence, we asked whether aluminum hydroxide allows a better Th1 immune deviation than aluminum phosphate. We also studied several ways to mix the antigens and the impact on CR3-specific interferon (IFN)-gamma secretion. Our findings indicate that aluminum hydroxide allows better Th1 immunodeviation than aluminum phosphate adjuvant for the mixture of HBV antigens and CR3. In addition, CR3-specific IFN-gamma secretion of the various formulations tested was the same irrespective of the order in which the antigens were combined.

Profiles of NK, NKT cell activation and cytokine production following vaccination against hepatitis B.

Human natural killer (NK) cells (CD56+ CD3-) represent crucial components of the innate immune system especially against viral infections and because their activation can modulate the outcome of the adaptive immune response. NKT cells (CD56+CD3+), a lymphocyte T population characterized by expression of surface markers of NK cells, are known to be abundant in the liver and their activation could be associated with hepatic injury. Using three-color flow cytometry to measure surface receptors and intracellular cytokines, we have explored early activation signals and cytokine production in NK and NKT cells within a group of hepatitis B vaccinated and non-vaccinated individuals. A specific increase of the CD56bright cell population, the activation receptor CD69 and IFN-gamma, was observed in NK cells following incubation with recombinant HBsAg in responders to vaccination. Comparable results were observed in NKT cells showing an increment of CD69, CD25, IL-2 and IFN-gamma expression in responder subjects. These parameters were statistically diminished in non-responder individuals (p<0.05) in both groups of cells. These results demonstrate a diminished activation of these cells in non-responders to the vaccine, suggesting that NK and NKT cells play an important role in the immune response following hepatitis B vaccination.

Development of a nasal vaccine for chronic hepatitis B infection that uses the ability of hepatitis B core antigen to stimulate a strong Th1 response against hepatitis B surface antigen.

There are estimated to be 350 million chronic carriers of hepatitis B infection worldwide. Patients with chronic hepatitis B are at risk of liver cirrhosis with associated mortality because of hepatocellular carcinoma and other complications. An important goal, therefore, is the development of an effective therapeutic vaccine against chronic hepatitis B virus (HBV). A major barrier to the development of such a vaccine is the impaired immune response to HBV antigens observed in the T cells of affected patients. One strategy to overcome these barriers is to activate mucosal T cells through the use of nasal vaccination because this may overcome the systemic immune downregulation that results from HBV infection. In addition, it may be beneficial to present additional HBV epitopes beyond those contained in the traditional hepatitis B surface antigen (HbsAg) vaccine, for example, by using the hepatitis B core antigen (HBcAg). This is advantageous because HBcAg has a unique ability to act as a potent Th1 adjuvant to HbsAg, while also serving as an immunogenic target. In this study we describe the effect of coadministration of HBsAg and HBcAg as part of a strategy to develop a more potent and effective HBV therapeutic vaccine.

[Association of humans leucocitary antigens with humoral nonresponsive to hepatitis B vaccine in chronic hemodialysis patients]. / Associação dos antígenos leucocitários humanos com a ausência de resposta humoral à vacina da hepatite B em pacientes renais crônicos hemodialisados.

Vaccination using surface antigen from hepatitis B virus has not been successfully responded by hemodialysis patients. The present study was aimed at assessing a possible relationship between human leukocyte antigens and the low production of protective antibodies (anti-HbS) against the surface antigen from hepatitis B by patients with chronic renal failure submitted to hemodialysis programs. The antigens HLA-DR and HLA-DQ were identified in 76 hemodialysis patients through classic microlymphotoxicity. Our results showed that 34.2% of the patients were non-responsive to the vaccine VHB. The most frequent HLA specificity were: HLA-DR3, DR-7 and DQ2 with a significant association for HLA-DR3 (p=0.0025; OR 5.1; IC 95% 1.36-19.10). Such data suggest an association between genes from HLA class II antigens and the humoral non-response to the vaccine VHB.

Inmunogenicidad de la vacuna recombinante cubana contra la Hepatitis B en trabajadores de la salud del Instituto Peruano de Seguridad Social / Inmunogenicity of the cuban recompunded vaccine against type B hepatitis in public health workers of the IPSS

Se investigó la inmunogenicidad (seroconversión, seroprotección hiperrespuesta y media geométrica) producida por la vacuna recombinante cubana contra la hepatitis viral tipo B en nuestro medio, en un estudio multicentrico nacional, concurrente, aplicando el sistema de 0, 1, 2 meses en 211 trabajadores de la salud, susceptibles, pertenecientes al IPSS. La cuantificación del antiHBs se realizó por el método inmunoenzimático de Organon Tecknics. Se obtuvo un 97 por ciento de seroprotección en solo 75 días de haber iniciado el esquema, observandose una mayor inmunogenicidad en mujeres menores de 40 años. Se recomienda la aplicación de este esquema como parte del programa de control en la Hepatitis viral tipo B por su simetría, corta latencia y grado de protección

[Comparative efficacy of intradermal and intramuscular active immunization against hepatitis B with a recombinant vaccine. Preliminary results]. / Eficacia comparativa de las vías intradérmica e intramuscular en la inmunización activa contra la hepatitis B con una vacuna recombinante. Resultados preliminares.

Preliminary results of a prospective, comparative and randomized study on 119 sero-negative volunteers with increased risk to acquire hepatitis B, aimed to evaluate the comparative efficacy of a recombinant vaccine administered either intramuscularly or intradermally, are discussed. A short vaccination schedule of three consecutive doses given on months 0, 1 and 2 was used. Distribution by sex and age for both groups was similar. Seroconversion and seroprotection rates were comparable (96% and 96% Vs. 98% and 93%, respectively). The geometric mean titre of anti-HBsAg in individuals immunized via I.M. (155 IU/L) was significantly higher to that of the I.D. group (71 IU/L). On the other hand, the rate of good response (> 100 IU/L) was also higher in the I.M. group (67% Vs. 39%). The percentage of good responder in women was consistently higher than in men for both groups (75% Vs. 13%, respectively). In 68 vaccinees, samples were obtained one year later. The levels of anti-HBsAg and the anamnesic response after a booster of the vaccine are currently being assayed.

Respuesta de sujetos sanos a la vacuna anti-hepatitis B plasmo-derivada / Response of healthy subjects to plasma - derived antihepatitis B vaccine -derived

Se presenta una serie de 71 sujetos sanos vacunados con 60 mcgrs de antígeno de superficie del virus B de hepatitis, extraido de plasma de portadores crónicos e inactivado con formalina y calor. La vacuna produjo niveles protectores de anticuerpos contra el antígeno de superficie (> 10 mUl/ml) en el 94.4 de los vacunados. Los efectos colaterales fueron escasos e irrelevantes (15.4%). El grupo de vacuandos que alcanzó títulos de anticuerpos superiores a 100 ml/ml tuvo una media de edad signficativamente menor que el de respuesta inferior a 100 mUl/ml. No hubo diferencia significativa entre las medias de superficie corporal de ambos grupos. Esto indica que el grado de respuesta se asocia con la edad y no con la superficie corporal

Respuesta de sujetos sanos a la vacuna anti-hepatitis B plasmo-derivada / Response of healthy subjects to plasma - derived antihepatitis B vaccine -derived

Se presenta una serie de 71 sujetos sanos vacunados con 60 mcgrs de antígeno de superficie del virus B de hepatitis, extraido de plasma de portadores crónicos e inactivado con formalina y calor. La vacuna produjo niveles protectores de anticuerpos contra el antígeno de superficie (> 10 mUl/ml) en el 94.4 de los vacunados. Los efectos colaterales fueron escasos e irrelevantes (15.4%). El grupo de vacuandos que alcanzó títulos de anticuerpos superiores a 100 ml/ml tuvo una media de edad signficativamente menor que el de respuesta inferior a 100 mUl/ml. No hubo diferencia significativa entre las medias de superficie corporal de ambos grupos. Esto indica que el grado de respuesta se asocia con la edad y no con la superficie corporal (AU)

[Response of healthy subjects to plasma-derived anti-hepatitis B vaccine]. / Respuesta de sujetos sanos a la vacuna anti-hepatitis B plasmo-derivada.

71 healthy individuals were vaccinated against hepatitis B virus. Each person received 60 mcgrs of HBsAg derived from chronic carriers heat-formalin treated plasma. All the vaccinees were tested for anti-HBs and 94.4% of them reached the protective titer (greater than 10 mUI/ml). There were few and no significant side effects (15.4%). Those vaccines with antibody titers higher than 100 mUI/ml were significantly younger than those with antibody titers lower than 100 mUI/ml. There was no significant difference between the body surface means of both groups. Thus, the vaccine level response is not associated with the body surface but with people's age.