Serologic response to hepatitis B vaccine with high dose and increasing number of injections in HIV infected adult patients

Sixty-five HIV-infected patients received high-dose (40mug), short interval HBV vaccine. In non-responders to the initial immunization, 1-3 boosters were administered. Rate of response was 60.0% after primary vaccination, and 89.2% after boosters. However, 12 and 24 months after the last vaccination, only 63% and 32.7% of the responders, respectively, had persistence of protective anti-HBs titers (> or =10 IU/L). The results of logistic regression show that gender, CD4 count, and HIV viral load were significant predictors of vaccination outcome. This study suggests that in HIV-infected patients with relatively high CD4 count, response to high dose of HBV vaccine is suboptimal. Rate of response may be increased by vaccine boosts, but antibody titers are significantly lower in non-responders than in responders to primary vaccination. Since persistence of anti-HBs titers appears significantly related to antibody titers after the immunization procedure, monitoring of anti-HBs, particularly in patients with low level of protective antibody titers after primary vaccination or boosters, seems more than justified.     

A randomised, double-blind, non-inferiority clinical trial on the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis (TdaP) vaccine in comparison to a tetanus and diphtheria (Td) vaccine when given as booster vaccinations to healthy adults

Background

Increasing incidence of pertussis in adolescents and adults has stimulated the development of safe and immunogenic acellular pertussis vaccines for booster vaccination of adolescents and adults.

Purpose

To obtain clinical documentation of the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis combination vaccine (TdaP), when given as a booster vaccination to adults.

Methods

The trial was double-blind, controlled and randomised. 802 healthy adults, aged 18–55 years who had completed childhood vaccination with diphtheria, tetanus and whole cell pertussis vaccine (DTwP), were booster vaccinated with TdaP or Td. Blood samples were taken before and one month after the vaccination for serological analysis and adverse events were recorded during the one-month-follow-up period.

Results

The monocomponent acellular pertussis vaccine (aP) in the TdaP vaccine was immunogenic in adults with 92.0% of TdaP vaccinated subjects obtaining an anti-pertussis toxin (anti-PT) antibody booster response. TdaP was non-inferior to Td in eliciting seroprotective anti-tetanus and diphtheria antibody concentrations with more than 98% of subjects obtaining post-vaccination seroprotective concentrations (≥0.1 IU/mL). T and d booster response rates were 93.0% and 97.5%, respectively.The frequencies of solicited local adverse reactions were low and comparable between TdaP and Td vaccinees. In the TdaP group, 30.7% reported pain, 4.2% swelling and 2.0% erythema at the injection site. The most frequent solicited general symptoms were headache (20.4%), fatigue (17.0%) and myalgia (10.0%). In the Td group, 35.7% reported pain, 2.5% swelling and 3.2% erythema at the injection site, whereas headache, fatigue and myalgia were reported by 15.7%, 14.5% and 12.5%, respectively.In conclusion, TdaP Vaccine SSI was safe and immunogenic when given as a booster vaccination to adults. ClinicalTrials.gov registration number: NCT01033877.     

Pneumococcal polysaccharide 23-valent vaccine: long-term persistence of circulating antibody and immunogenicity and safety after revaccination in adults

Since publication of a 1997 review of the immunogenicity and safety data for pneumococcal polysaccharide vaccines (PPSVs), dozens of additional studies have been published, involving larger cohorts, longer observation periods, and more specific assays. Additionally, a 13-valent pneumococcal conjugate vaccine (PCV) has been licensed for adults. This paper reviews adult studies assessing antibody persistence for ≥ 3 years after pneumococcal vaccination, and adult studies of immunogenicity and safety after revaccination. This review emphasizes the currently registered PPSV23 formulations containing 25-μg polysaccharide per serotype, for which far more long-term data are available. Broadly, IgG and functional antibody levels after PPSV23 in adults persist above concentrations in unvaccinated adults for at least 5-10 years in most studies. The few exceptions involve populations of non-ambulatory adults or those with confounding host-factor issues. Revaccination with PPSV23 5-10 years after a previous dose consistently and substantially increases both IgG and functional antibody levels. There is an inverse association between circulating antibody level just before primary or revaccination and subsequent antibody increase. Although injection-site reactions (e.g., pain, swelling, redness) were reported more commonly after PPSV23 revaccination than after primary vaccination in most studies, these reactions typically resolved within 5 days. We interpret the contemporary literature as supporting pneumococcal revaccination as a means to sustain anti-pneumococcal antibodies at levels greater than among unvaccinated adults. PPSV23 is a broad-spectrum public-health tool to help prevent serious pneumococcal diseases across the adult lifespan.     

e抗原阳性产妇之婴儿对国产血源乙型肝炎疫苗免疫应答三年观察结果

本文报告了73例接种国产乙型肝炎疫苗的e抗原阳性产妇之婴儿,其乙肝表面抗体滴度动态及免疫应答持续情况的三年观察结果。同时,对再接种问题进行了讨论。     

Induction of systemic and mucosal immunity and maintenance of its memory against influenza A virus by nasal vaccination using a new mucosal adjuvant SF-10 derived from pulmonary surfactant in young cynomolgus monkeys

Induction of systemic and mucosal immunity and maintenance of its memory was investigated in 12 young male cynomolgus monkeys after intranasal instillation of flu vaccine using a new mucosal adjuvant SF-10 derived from pulmonary surfactant constituents. Split-product of influenza virus A/California/7/2009(H1N1)pdm hemagglutinin vaccine (HAv) at 15 μg with or without SF-10 and the adjuvant alone were instilled intranasally three times every 2 weeks. SF-10-adjuvanted HAv (SF-10-HAv) elicited significantly higher HAv-specific IgG and hemagglutinin inhibition (HI) titers in serum and HAv-specific secretory IgA and its neutralizing activities in nasal washes compared with HAv antigen and SF-10 alone. Significant cross-neutralizing activities of nasal washes after the third vaccination to several other H1N1 and H3N2 strains were observed. HI titers in serum and neutralizing activities in nasal washes reached peak levels at 6 weeks after initial vaccination, then gradually decreased after 10 weeks and returned to the baseline levels at 36 weeks. A single intranasal revaccination of SF-10-HAv at 36 weeks rapidly and significantly increased both immunity in serum and nasal washes compared with naïve monkeys. Revaccination by one or two doses achieved almost maximal immunity at 2 or 4 weeks after instillation. Statistically significant adverse effects (e.g., body weight loss, elevated body temperature, nasal discharge, change in peripheral blood leukocyte and platelet counts) were not observed for 2 weeks after vaccination of SF-10-HAv, HAv or SF-10 and also during the experimental period. These results in young monkey model suggest the potential of clinical use SF-10 for intranasal flu vaccine.     

The challenge of improving the efficacy of measles vaccine

Despite a safe and effective measles vaccine, measles still claims an estimated 800,000 lives per year mostly among children in developing countries. This paper deals with strategies to improve vaccine efficacy and prevent unnecessary deaths, including considerations of one dose at 9 months strategy for developing countries, strain of vaccine, potency and number of doses of measles vaccine. After more than 20 years of measles immunisation in the developing world, the epidemiology of measles is radically changed, and the absence of measles epidemics might lead to waning immunity due to less clinical and subclinical infections boosting the antibody level. An increasing proportion of mothers are vaccinated, thus transferring a lower maternal antibody level to their infants who will be susceptible to measles at a younger age. The strategies to limit nosocomial measles infection and spread of measles epidemics are reviewed. Though the measles elimination programmes have been very effective in the Americas, it seems unlikely that they will be equally effective in the rest of the world. Even if eradication should be possible, it might be unwise to stop measles vaccination because the vaccine apparently has beneficial effects and because it would make measles a likely weapon for bio-terrorism. If we are unlikely to get rid of measles and measles vaccine, it might be wise to study further some of the many unanswered questions regarding the long-term effects of measles and measles vaccination.     

乙肝酵母基因疫苗免疫后抗-HBs下降规律及推测加强免疫时间的探讨

200名HBV易感者分二组分别接种Amgen公司生产的乙肝酵母基因疫苗(G苗)和Smith公司疫苗(s苗).4年后24.59％的免疫者抗-HBs滴度下降到10mlU/ml以下。抗-HBs保护水平持续时间取决于3针免疫后最高滴度水平。抗-HBs>1000mlU/ml者,4年后G苗仍100％大于10mlU/ml,S苗则为97.6％,而抗-HBs在10～100mIU/ml之间者,4年后皆<10mIU/nl。抗-HBs滴度随时间延长呈指数曲线下降,首次免疫后前24个月几乎下降了全部滴度的80％,以后下降缓慢,抗-HBs滴度水平不同组其回归直线斜率相似,表明抗-HBs滴度下降百分率与最初浓度无关。在此基础上制出标准回归直线,并用做平行线的方法推测个体加强免疫时间。     

接种乙型肝炎疫苗无应答儿童复种后5年效果观察

目的评价乙型肝炎（乙肝）疫苗无应答儿童复种远期效果并比较小剂量皮内与常规剂量肌肉复种效果。方法自2000年10月开始，40名经筛检获得的无应答健康儿童随机接受3针肌肉（17人，10μg/针）或皮内（23人，2μg/针）复种，定期采血检测至复种后5年；80名应答儿童不复种，作为同期观察对照。在第5年，评价HB-sAg特异性淋巴细胞免疫水平；对抗-HBs阴转者加强1针（5μg），12-14d评价抗体回忆应答。结果仅1名皮内复种者抗-HBs未达到10IU／L；在第5年，50％的肌肉复种者仍保持着抗-HBs≥10IU／L（尽管该指标显著低于应答对照者的85％）。抗-HBs阴转者（肌肉，皮内复种和应答对照分别为8、18和11人）再加强1针后，除2名皮内复种者外，均产生了强劲的抗体回忆应答（抗-HBs滴度分别平均上升至208、105和549IU／L）；超过70％的无应答儿童外周血单个核细胞可检测到HBsAg特异性白细胞介素（IL）-2和IL-5的分泌。用抗-HBc阳转作为感染指标计算乙肝病毒人年感染率，皮内复种者为8．9％（8／89．9人年），高于应答对照者的3．6％（12／337．2人年），而肌肉复种者为4．3％（3／70、2人年），与应答对照者接近。结论无应答儿童3针肌肉复种效果虽达不到应答儿童初种的水平，但确能发挥重要的免疫保护作用。小剂量皮内复种效果不如相同针次常规剂量肌肉复种。     

Sero-surveillance of Measles in Iranian Army Students after Nationwide Revaccination in 2004

Background: Decay of vaccine–induced antibody titres without boosting of the wild measles virus has been well documented. Revaccination against measles has reduced the prevalence of the disease worldwide. Revaccination may cause IgE induced anaphylaxis. Objective: To study measles IgG antibody in revaccinated populations and its relation to IgE induced hypersensitivity. Methods: Blood samples were taken from 800 volunteer army students aging from 18-22 years after one month of nationwide revaccination in Tehran in the year 2004. Sera were collected and kept frozen until used. Anti-measles IgG antibody and total IgE antibody were measured by ELISA assay. Results: Data indicated that only 2.37% of subjects were negative for measles antibody (titre less than 500) after a single dose of booster vaccination. From those individuals with positive IgG, 200 cases (25%) had antibody titres over 5000 IU/ml. The results showed a maximum IgE antibody titre of 1000 IU/ml (p<0.02) in which thirty cases (3.75%) had IgE titres over 1000 IU/ml (p<0.02). Conclusion: Single vaccination against measles during childhood is not sufficient for protecting against measles virus and revaccination is needed to recall specific immunity, although like other viral infections it may trigger IgE antibody responses in a small percentage of the population.     

T lymphocytes subsets and cytokine pattern induced by vaccination against bovine brucellosis employing S19 calfhood vaccination and adult RB51 revaccination

The aims of this study were to address the protective immune response induced by S19 vaccination (n = 10) and RB51 revaccination, in pregnant (n = 9) and non-pregnant (n = 10) S19 calfhood-vaccinated cattle as follows: evaluate the in vitro CD4⁺ and CD8⁺ T-lymphocytes specific proliferation, and in vitro expression of IFN-γ by CD4⁺ and CD8⁺ T-cells and IL-4 by CD4⁺, CD8⁺ and CD21⁺ lymphocytes subset. Upon in vitro stimulation with γ-irradiated Brucella abortus 2308, blood mononuclear cells from S19 vaccinated and RB51 revaccinated cows exhibited significantly higher proliferation of CD4⁺ and CD8⁺ T-lymphocytes and CD4⁺IFN-γ⁺ T-cells compared to non-vaccinated animals. RB51 revaccination, regardless of the pregnancy status, did not enhance the proliferation of CD4⁺ or CD8⁺ T-cells nor IFN-γ or IL-4 production. Data from the present study suggest that cattle's cellular immune response induced after brucellosis vaccination and revaccination is due to CD4⁺ and CD8⁺ T-lymphocytes, being CD4⁺ T-cells the main source of IFN-γ.