乙型肝炎疫苗与卡介苗、百白破混合菌苗的联合免疫效果观察

本文报道150名HBsAg阴性产妇所生新生儿在实施计划免疫的同时,1、2组分别接种10μg、20μg乙肝疫苗,3组不接种乙肝疫苗,以了解乙肝疫苗与卡介苗、百白破联合免疫的免疫应答。结果表明:1.2组抗-HBc达到有效保护的(P/N≥5)为93.18％和89.58％,无显著差异;两组均未检出HBV标志物,但是未注射乙肝疫苗组HBV感染达6.67％。乙肝疫苗与卡介苗、百白破联合免疫应答是好的,抗原间无干扰,从而证明乙肝疫苗不但能有效地控制乙型肝炎,并能纳入扩大免疫规划。     

新生儿接种两种剂型乙型肝炎疫苗不同时间的免疫水平比较

目的:研究接种两种不同剂型的乙肝疫苗(Hepatitis B vaccine,Hep B)(包括10μg CHO基因工程乙肝疫苗(以下简称10μg Hep B)与5μg重组酵母乙肝疫苗(以下简称5μg Hep B))后不同时间,新生儿体内免疫水平的变化,为新生儿乙肝疫苗的接种提供科学依据。方法:选择2016年7月1日-2018年12月1日在青岛大学附属医院接种且按照0、1、6个月免疫程序完成乙型肝炎疫苗全程接种的,采用化学放光法测定血清中抗体水平,比较接种10μg与5μg Hep B后不同时间新生儿体内抗体变化。结果:接种1、6和12月后,10μg Hep B组新生儿低无应答率显著低于5μg Hep B组,而肝表面抗体滴度明显高于5μg Hep B组(P0.05);12个月后,两组新生儿乙肝表面抗体滴度均呈现下降趋势;10μg Hep B组新生儿乙肝表面抗体阳性率仍显著高于5μg Hep B组(P0.05)。结论:新生儿接种10μg Hep B的免疫效果优于5μg Hep B。     

乙型肝炎疫苗与卡介苗、百白破、脊髓灰质炎疫苗联合免疫的免疫应答观察

本文报道在对婴幼儿实施基础免疹(BCC、DPT和TOPV)的同时,接种国产血源乙肝疫苗的免疫应答。对八月龄的婴儿血清学检测结果表明:乙肝疫苗接种组1(10μg)、2(20μg)抗-HBs达到临界保护(P/N≥10.0)的分别为80.65％,78.49％,未检出HBV感染标志物;未接种乙肝疫苗组的HBV感染率边10.5％。血清学检测还表明乙肝疫苗与BCG、DPT和TOPV等生物制品联合免疫应答是好的,各抗原间无干扰作用,提示乙肝疫苗可列入扩大免疫规划,并将有效地控制乙肝病毒感染。     

Effect of a booster dose of serogroup B meningococcal vaccine on antibody response to Neisseria meningitidis in mice vaccinated with different immunization schedules

The generation and maintenance of memory antibody response by different primary immunization schedules with the Cuban-produced outer membrane protein based vaccine was investigated in a murine model. We analyzed the duration of the antibody response (IgG-ELISA and bactericidal titer) and the effect of a booster dose on the antibody response. The IgG avidity index was determined in an attempt to find a marker for memory development. This study also included an analysis of IgG subclasses induced by primary and booster immunization. The specificity of bactericidal antibodies was investigated using local strains of the same serotype/serosubtype (4,7:P1.19,15) as the vaccine strain and mutant strains lacking major outer membrane proteins. A significant recall response was induced by a booster dose given 7 months after a primary series of 2, 3 or 4 doses of vaccine. The primary antibody response showed a positive dose-effect. In contrast, a negative dose-effect was found on the booster bactericidal antibody response. There was a significant increase in IgG1 levels after the fourth and booster doses. Three doses of vaccine were required to induce a significant increase in IgG avidity. Two injections of vaccine induced a significant antibody response to PorA protein, while 4 injections induced a larger range of specificities.     

Protective effect of hepatitis B vaccine combined with two-dose hepatitis B immunoglobulin on infants born to HBsAg-positive mothers

Background

Despite the use of hepatitis B (HB) vaccine and hepatitis B immunoglobulin (HBIG), a portion of infants are still non- or low-responders, or even immunoprophylaxis failure. We aimed to determine the immune response in the infants from the mothers being positive for hepatitis B surface antigen (HBsAg), by which the infants received three doses of HB vaccine in combination with two-dose 200 IU HBIG injections.

Methods

In this retrospective study, 621 infants from HBsAg-positive mothers in Beijing YouAn Hospital between January 2008 and December 2009 were included. All the infants were given three doses of 10 µg HB vaccine (at 0, 1 and 6 months of age) and two-dose of 200 IU HBIG (at birth and in 2 weeks of age). Serum HBsAg and antibody to HBsAg (anti-HBs) in all the infants were determined at 7 months of age.

Results

Of the 621 infants, 2.9% were immunoprophylaxis failure (positive for HBsAg), 1.4% were non-responders (anti-HBs undetectable), 95.7% were responders. The 594 responders could be categorized into three subsets, 22 were 10 to 99 IU/L for anti-HBs levels, 191 were 100 to 999 IU/L, and 381 were ≥1000 IU/L. The immunoprophylaxis failure rate was at 0% and 5.2% for the infants of HBeAg-negative and HBeAg-positive mothers(P<0.001). Infants from mothers with detectable HBV DNA had higher incidence of immunoprophylaxis failure than those of mothers without detectable HBV DNA (P = 0.002). The factors including gender, birth weight, gestation weeks, the rates of maternal HBeAg-positive, and detectable HBV DNA did not contribute to the no response to HB vaccination.

Conclusions

Through vaccination by three doses of HB and two-dose of HBIG, majority of the infants (95.7%) achieved a protective level of anti-HBs at 7 months of age. Maternal HBeAg-positive and HBV DNA detectable were associated with the immunoprophylaxis failure, but not contribute to the non- or low-response to HB vaccination.     

The magnitude of the antibody and memory B cell responses during priming with a protein-polysaccharide conjugate vaccine in human infants is associated with the persistence of antibody and the intensity of booster response

Rapid waning of anti-polysaccharide bactericidal Ab and vaccine effectiveness is observed following infant immunization with the serogroup C meningococcal (MenC) glycoconjugate vaccine. This is despite the demonstrable presence of immunological memory. Persistence of functional Ab, therefore, appears to be the key determinant of MenC conjugate vaccine effectiveness. Ab persistence is thought to depend in the short term on the survival of plasma cells generated during priming and in the longer term on the production of new Ab secreting cells from memory B cells. In this study, we found a strong association between the level of MenC-specific Ab and the frequency of memory B cells measured at 5 mo of age (1 mo after 3-dose primary immunization with MenC conjugate vaccine), and the persistence of functional Ab at one year of age. These findings suggest that these two parameters are good markers of B cell responses to priming and can be used as predictors of long term humoral immunity induced by glycoconjugate vaccines received in early infancy.     

Differential effect of TLR2 and TLR4 on the immune response after immunization with a vaccine against Neisseria meningitidis or Bordetella pertussis

Neisseria meningitidis and Bordetella pertussis are Gram-negative bacterial pathogens that can cause serious diseases in humans. N. meningitidis outer membrane vesicle (OMV) vaccines and whole cell pertussis vaccines have been successfully used in humans to control infections with these pathogens. The mechanisms behind their effectiveness are poorly defined. Here we investigated the role of Toll-like receptor (TLR) 2 and TLR4 in the induction of immune responses in mice after immunization with these vaccines. Innate and adaptive immune responses were compared between wild type mice and mice deficient in TLR2, TLR4, or TRIF. TRIF-deficient and TLR4-deficient mice showed impaired immunity after immunization. In contrast, immune responses were not lower in TLR2-/- mice but tended even to be higher after immunization. Together our data demonstrate that TLR4 activation contributes to the immunogenicity of the N. meningitidis OMV vaccine and the whole cell pertussis vaccine, but that TLR2 activation is not required.     

Suppression and augmentation of the primary in vitro immune response by different classes of antibodies

The capacity of purified γG₁ and γG₂ anti-sheep red blood cell (SRBC) antibodies to exert antigen-specific feedback regulations on the primary in vitro immune response to SRBC was studied. Antibodies were administered to the culture in the native form, as sheep erythrocyte-antibody complexes or as pepsin-derived F(ab′)₂ antibody fragments. Marked differences in the feedback regulatory effects of γG₁ and γG₂ antibodies were found. Antibodies of the γG₁ class suppressed the immune response to SRBC, whereas γG₂ antibodies isolated from the same serum exerted an augmenting effect on antibody synthesis. These opposing feedback effects on in vitro antibody synthesis were immunologically specific, relatively insensitive to changes in antigen concentrations, and could be elicited by either adding antibodies and antigen separately to the culture or as preformed antigen-antibody complexes. Experiments comparing the activities of the F(ab′)₂ antibody fragments with the parent γG₁ and γG₂ antibodies suggested that the Fc fragments may be involved in these regulatory effects on the immune response. It is concluded that the antigen-specific suppressive and augmenting effects on antibody synthesis shown here are determined by the antibody class. In addition, we suggest that these opposing antibody-mediated feedback effects may represent one of the important elements of the immune response.     

Protective immune response against cutaneous leishmaniasis by prime/booster immunization regimens with vaccinia virus recombinants expressing Leishmania infantum p36/LACK and IL-12 in combination with purified p36

In susceptible mice Leishmania infection triggers a CD4(+) Th2 response that has been correlated with evasion of the host immune system. To develop approaches that might trigger a Th1 response leading to protection against Leishmania we generated vaccinia virus recombinants (VVr) expressing the relevant p36/LACK protein of Leishmania infantum (VVp36) or co-expressing p36/LACK and interleukin-12 (VVp36IL12). Susceptible BALB/c mice were immunized with the VVr in various prime/booster protocols that included purified p36/LACK protein, followed 3 weeks later by a challenge with live L. major promastigotes. The course of the infection was monitored by measuring lesion development, parasite load and immunological parameters (IFN-gamma and IL-10 secretion by in vitro-stimulated lymphocytes, and specific IgG isotypes), before and after challenge. We found protocols of prime/booster immunization (VVp36/VVp36; VVp36IL12/p36; p36/VVp36IL12) that elicited different levels of protection in infected animals. The protocol of priming with purified p36 followed by a booster with VVp36IL12 induced 52% reduction in lesion size and a two-log unit reduction in parasite load. This partial protection correlated with activation of a specific Th1 type of immune response. These protocols could be of interest in the prophylaxis against Leishmania spp. and other parasitic diseases.