Prevention of congenital rubella.

The vaccine of choice for rubella vaccination is considered to be RA 27/3, based on frequency of side effects, duration of immunity, antigenic potential and rate of reinfection by wild virus. The most appropriate individuals to be vaccinated are prepubertal schoolgirls and susceptible members of other high-risk groups, and a nationwide immunization program is suggested. Premarital determination of rubella-immune status should be mandatory for all women of childbearing age. A favourable cost/benefit ratio for rubella vaccination seems highly probable. The use of a rubella "fact sheet" to provide education and information for those at risk is strongly recommended.     

AIDS Prevention and Control in Japan

Surveillance for the acquired immunodeficiency syndrome (AIDS) in Japan started in September 1984 and in February 1987 was extended to seropositive carriers of human immunodeficiency virus (HIV) antibodies. A total of 2,000 hospitals and clinics throughout the country have actively participated in the surveillance. An educational program for health care workers, including physicians, was initiated in July 1985 by issuing a series of government memoranda and distributing pamphlets and posters. Counseling programs for people concerned about AIDS and laboratory support to provide screening services have been developed. Laboratories that can also perform confirmatory tests will be established shortly. The screening of all donated blood was established in November 1986.Education programs for the public have been conducted mainly through the production and distribution of various materials and pamphlets. Research has been focused primarily on diagnosis and treatment, with international cooperation emphasized. A new act of legislation has been proposed in the Parliament that will require mandatory reporting of cases of AIDS and HIV infection with confidentiality preserved. Further debate may be needed to reach national consensus on this issue. The proposed law will not include provisions that would affect international travelers, foreign students or immigrants.     

Effect of selective vaccination on rubella susceptibility and infection in pregnancy.

The effect of school and adult vaccination on susceptibility to rubella in women of childbearing age was assessed in the Manchester area, where the population attending antenatal clinics is over 40 000 a year. Between 1979 and 1984 the proportion susceptible fell from 6.4% to 2.7%. In 1984, 4.2% of nulliparous women were susceptible compared with 1.4% of women in their second or subsequent pregnancy. Eighty five per cent of pregnant women screened and found to be non-immune were vaccinated post partum before leaving hospital. Requests for prevaccination screening of non-pregnant women increased in response to a national campaign and at the time of local outbreaks of rubella but only two thirds of those found to be nonimmune were subsequently vaccinated. During 1983 and 1984 infection was confirmed in 57 pregnant women--2% of those non-immune. Selective vaccination has reduced susceptibility to rubella in the childbearing population, but it is suggested that mass vaccination of children of both sexes should be added to the existing policy to control circulation of wild rubella virus and reduce the risk of infection to pregnant women who remain susceptible.     

The use of an E1-deleted, replication-defective adenovirus recombinant expressing the rabies virus glycoprotein for early vaccination of mice against rabies virus.

An E1-deleted, replication-defective adenovirus recombinant of the human strain 5 expressing the rabies virus glycoprotein, termed Adrab.gp, was tested in young mice. Mice immunized at birth with the Adrab.gp construct developed antibodies to rabies virus and cytokine-secreting lymphocytes and were protected against subsequent challenge. Maternal immunity to rabies virus strongly interferes with vaccination of the offspring with a traditional inactivated rabies virus vaccine. The immune response to the rabies virus glycoprotein, as presented by the Adrab.gp vaccine, on the other hand, was not impaired by maternal immunity. Even neonatal immunization of mice born to rabies virus-immune dams with Adrab.gp construct resulted in a long-lasting protective immune response to rabies virus, suggesting that this type of vaccine could be useful for immunization shortly after birth. Nevertheless, pups born to Adrab.gp virus-immune dams showed an impaired immune response to the rabies virus glycoprotein upon vaccination with the Adrab.gp virus, indicating that maternal immunity to the vaccine carrier affected the offspring's immune response to rabies virus.     

Limited maintenance of vaccine-induced simian immunodeficiency virus-specific CD8 T-cell receptor clonotypes after virus challenge

T-cell receptors (TCRs) govern the specificity, efficacy, and cross-reactivity of CD8 T cells. Here, we studied CD8 T-cell clonotypes from Mane-A*10(+) pigtail macaques responding to the simian immunodeficiency virus (SIV) Gag KP9 epitope in a setting of vaccination and subsequent viral challenge. We observed a diverse TCR repertoire after DNA, recombinant poxvirus, and live attenuated virus vaccination, with none of 59 vaccine-induced KP9-specific TCRs being identical between macaques. The KP9-specific TCR repertoires remained diverse after SIV or simian-human immunodeficiency virus challenge but, remarkably, exhibited substantially different clonotypic compositions compared to the corresponding populations prechallenge. Within serial samples from individual pigtail macaques, only a small subset (33.9%) of TCRs induced by vaccination were maintained or expanded after challenge. Most (66.1%) of the TCRs induced by vaccination were not detectable after challenge. Our results suggest that some CD8 T cells induced by vaccination are more efficient than others at responding to a viral challenge. These findings have implications for future AIDS virus vaccine studies, which should consider the "fitness" of vaccine-induced T cells in order to generate robust responses in the face of virus exposure.     

A new generation of modified live-attenuated avian influenza viruses using a two-strategy combination as potential vaccine candidates

In light of the recurrent outbreaks of low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI), there is a pressing need for the development of vaccines that allow rapid mass vaccination. In this study, we introduced by reverse genetics temperature-sensitive mutations in the PB1 and PB2 genes of an avian influenza virus, A/Guinea Fowl/Hong Kong/WF10/99 (H9N2) (WF10). Further genetic modifications were introduced into the PB1 gene to enhance the attenuated (att) phenotype of the virus in vivo. Using the att WF10 as a backbone, we substituted neuraminidase (NA) for hemagglutinin (HA) for vaccine purposes. In chickens, a vaccination scheme consisting of a single dose of an att H7N2 vaccine virus at 2 weeks of age and subsequent challenge with the wild-type H7N2 LPAI virus resulted in complete protection. We further extended our vaccination strategy against the HPAI H5N1. In this case, we reconstituted an att H5N1 vaccine virus, whose HA and NA genes were derived from an Asian H5N1 virus. A single-dose immunization in ovo with the att H5N1 vaccine virus in 18-day-old chicken embryos resulted in more than 60% protection for 4-week-old chickens and 100% protection for 9- to 12-week-old chickens. Boosting at 2 weeks posthatching provided 100% protection against challenge with the HPAI H5N1 virus for chickens as young as 4 weeks old, with undetectable virus shedding postchallenge. Our results highlight the potential of live att avian influenza vaccines for mass vaccination in poultry.     

Evaluation of rubella screening in pregnant women

BACKGROUND: The rationale for rubella vaccination in the general population and for screening for rubella in pregnant women is the prevention of congenital rubella syndrome. The objective of this study was to evaluate the effectiveness of the prenatal rubella screening program in Quebec. METHODS: A historical cross-sectional study was designed. Sixteen hospitals with obstetric services were randomly selected, 8 from among the 35 "large" hospitals in the province (500 or more live births/year) and 8 from among the 50 "small" hospitals (fewer than 500 live births/year). A total of 2551 women were randomly selected from all mothers of infants born between Apr. 1, 1993, and Mar. 31, 1994, by means of stratified 2-stage sampling. The proportions of women screened and vaccinated were ascertained from information obtained from the hospital chart, the physician''s office and the patient. RESULTS: The overall (adjusted) screening rate was 94.0%. The rates were significantly different between large and small hospitals (94.4% v. 89.6%). Five large hospitals and one small hospital had rates above 95.0%. The likelihood of not having been screened was statistically significantly higher for women who had been pregnant previously than for women pregnant for the first time (4.8% v. 1.4%; p < 0.001). Of the 200 women who were seronegative at the time of screening (8.4%), 79 had been vaccinated postpartum, had a positive serological result on subsequent testing or did not require vaccination, and 59 had not been vaccinated postpartum; for 62, subsequent vaccination status was unknown. INTERPRETATION: Continued improvement in screening practices is needed, especially in small hospitals. Because vaccination rates are unacceptably low, it is crucial that steps be taken to address this issue.     

Cost-effectiveness of dengue vaccination in Puerto Rico

An effective and widely used vaccine could reduce the burden of dengue virus (DENV) around the world. DENV is endemic in Puerto Rico, where the dengue vaccine CYD-TDV is currently under consideration as a control measure. CYD-TDV has demonstrated efficacy in clinical trials in vaccinees who had prior dengue virus infection. However, in vaccinees who had no prior dengue virus infection, the vaccine had a modestly elevated risk of hospitalization and severe disease. The WHO therefore recommended a strategy of pre-vaccination screening and vaccination of seropositive persons. To estimate the cost-effectiveness and benefits of this intervention (i.e., screening and vaccination of seropositive persons) in Puerto Rico, we simulated 10 years of the intervention in 9-year-olds using an agent-based model. Across the entire population, we found that 5.5% (4.6%-6.3%) of dengue hospitalizations could be averted. However, we also found that 0.057 (0.045–0.073) additional hospitalizations could occur for every 1,000 people in Puerto Rico due to DENV-naïve children who were vaccinated following a false-positive test results for prior exposure. The ratio of the averted hospitalizations among all vaccinees to additional hospitalizations among DENV-naïve vaccinees was estimated to be 19 (13–24). At a base case cost of vaccination of 382 USD, we found an incremental cost-effectiveness ratio of 122,000 USD per QALY gained. Our estimates can provide information for considerations to introduce the CYD-TDV vaccine in Puerto Rico.     

Study of allergic reactions in the body after experimental smallpox vaccination

Experiments on guinea pigs demonstrated a mixed cellular-humoral character of allergy in smallpox vaccination. The ratio of cellular and humoral components depended on the site of the vaccina application. Skin manifestations in smallpox vaccination (hyperemia, infiltration, papula) were due to the multiplication of the virus proper, increased sensitivity of the surrounding tissues to the live vibrio, and specific immunological reconstruction. The skin of the sensitized animal after the anaphylactic shock in response to the intracardiac injection of the challenging dose of the vaccine virus acquired areactivity to its subsequent application.     

Hepatitis B Screening and Vaccination Strategies for Newly Arrived Adult Canadian Immigrants and Refugees: A Cost-Effectiveness Analysis

Background

Immigrants have increased mortality from hepatocellular carcinoma as compared to the host populations, primarily due to undetected chronic hepatitis B virus (HBV) infection. Despite this, there are no systematic programs in most immigrant-receiving countries to screen for chronic HBV infection and immigrants are not routinely offered HBV vaccination outside of the universal childhood vaccination program.

Methods and findings

A cost-effective analysis was performed to compare four HBV screening and vaccination strategies with no intervention in a hypothetical cohort of newly-arriving adult Canadian immigrants. The strategies considered were a) universal vaccination, b) screening for prior immunity and vaccination, c) chronic HBV screening and treatment, and d) combined screening for chronic HBV and prior immunity, treatment and vaccination. The analysis was performed from a societal perspective, using a Markov model. Seroprevalence estimates, annual transition probabilities, health-care costs (in Canadian dollars), and utilities were obtained from the published literature. Acute HBV infection, mortality from chronic HBV, quality-adjusted life years (QALYs), and costs were modeled over the lifetime of the cohort of immigrants. Costs and QALYs were discounted at a rate of 3% per year. Screening for chronic HBV infection, and offering treatment if indicated, was found to be the most cost-effective intervention and was estimated to cost $40,880 per additional QALY gained, relative to no intervention. This strategy was most cost-effective for immigrants < 55 years of age and would cost < $50,000 per additional QALY gained for immigrants from areas where HBV seroprevalence is ≥ 3%. Strategies that included HBV vaccination were either prohibitively expensive or dominated by the chronic HBV screening strategy.

Conclusions

Screening for chronic HBV infection from regions where most Canadian immigrants originate, except for Latin America and the Middle East, was found to be reasonably cost-effective and has the potential to reduce HBV-associated morbidity and mortality.     

Protective Vaccination against Infectious Bursal Disease Virus with Whole Recombinant Kluyveromyces lactis Yeast Expressing the Viral VP2 Subunit

Here we report on vaccination approaches against infectious bursal disease (IBD) of poultry that were performed with complete yeast of the species Kluyveromyces lactis (K. lactis). Employing a genetic system that enables the rapid production of stably transfected recombinant K. lactis, we generated yeast strains that expressed defined quantities of the virus capsid forming protein VP2 of infectious bursal disease virus (IBDV). Both, subcutaneous as well as oral vaccination regiments with the heat-inactivated but otherwise untreated yeast induced IBDV-neutralizing antibodies in mice and chickens. A full protection against a subsequent IBDV infection was achieved by subcutaneous inoculation of only milligram amounts of yeast per chicken. Oral vaccination also generated protection: while mortality was observed in control animals after virus challenge, none of the vaccinees died and ca. one-tenth were protected as indicated by the absence of lesions in the bursa of Fabricius. Recombinant K. lactis was thus indicated as a potent tool for the induction of a protective immune response by different applications. Subcutaneously applied K. lactis that expresses the IBDV VP2 was shown to function as an efficacious anti-IBD subunit vaccine.     

Targeting of Non-Dominant Antigens as a Vaccine Strategy to Broaden T-Cell Responses during Chronic Viral Infection

In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes facilitates potent virus-induced T-cell responses against immunodominant epitopes during subsequent challenge with highly invasive virus. In contrast, when an immunodominant epitope was included in the vaccine, the T-cell response associated with viral challenge remained focussed on that epitope. Early after challenge with live virus, the CD8+ T cells specific for vaccine-encoded epitopes, displayed a phenotype typically associated with prolonged/persistent antigenic stimulation marked by high levels of KLRG-1, as compared to T cells reacting to epitopes not included in the vaccine. Notably, this association was lost over time in T cells specific for the dominant T cell epitopes, and these cells were fully capable of expanding in response to a new viral challenge. Overall, our data suggests a potential for broadening of the antiviral CD8+ T-cell response by selecting non-dominant antigens to be targeted by vaccination. In addition, our findings suggest that prior adenoviral vaccination is not likely to negatively impact the long-term and protective immune response induced and maintained by a vaccine-attenuated chronic viral infection.     

Accuracy and repeatability of a micro plaque reduction neutralization test for vaccinia antibodies.

The detection of neutralizing antibodies against vaccinia virus is a valuable tool for the investigation of previous smallpox vaccination. Compulsory smallpox vaccination ended in Brazil during the early 1970s, although the vaccine was available until the late 1970s. The threat of smallpox as a biological weapon has called the attention of public health authorities to the need for an evaluation of the immune status of the population. Based on our previous experience with a micro plaque reduction neutralization test (PRNT) for the evaluation of yellow fever immunity, a similar test was developed for the detection and quantification of vaccinia neutralizing antibodies. A cross-sectional study to test the repeatability and validity of plaque reduction neutralization test (PRNT) for vaccinia antibodies was performed in 182 subjects divided into two categories: subjects above 31 years old and the other > or = 35 years old. Cases were subjects considered to have been vaccinated with vaccinia virus if they declared vaccination history or evidenced vaccination marks. The assay is carried out in 96-well plates, provides results within 30 h, is easily performed, has good sensitivity (92.7%) and specificity (90.8), excellent repeatability (ICC 0.89 (0.88; 0.92)) and is thus suitable for use in mass screening of a population's antibody levels.     

Multilevel Factors Influencing Hepatitis B Screening and Vaccination among Vietnamese Americans in Atlanta,Georgia

Chronic hepatitis B virus (HBV) infection may lead to liver cirrhosis, chronic liver disease, and liver cancer. Immunization rates are suboptimal among Asian Americans/Pacific Islanders (AAPIs), who remain disproportionately affected by these illnesses. We investigated socioecological factors affecting HBV prevention among 316 Vietnamese Americans in Atlanta, Georgia. Social and community support of HBV vaccination was associated with screening (OR=1.69, 95% CI [1.21,2.38]), vaccination (OR=1.89, [1.27,2.81]), and intent to vaccinate (OR=1.77, [1.13,2.78]). Misconceptions decreased screening likelihood (OR=0.67, [0.46,0.99]) and vaccination (OR=0.55, [0.35,0.86]). Those able to pay for medical treatment (OR=1.23, [1.01,1.50]) were also more likely immunized, and greater transportation access (OR=1.42, [1.07,1.87]) was associated with greater intention to vaccinate. Multi-level factors facilitated HBV vaccination in this population. Tailored, culturally appropriate communication strategies will positively influence immunization uptake.     

Vaccination alters the balance between protective immunity, exhaustion, escape, and death in chronic infections

While T cell-based vaccines have the potential to provide protection against chronic virus infections, they also have the potential to generate immunopathology following subsequent virus infection. We develop a mathematical model to investigate the conditions under which T cells lead to protection versus adverse pathology. The model illustrates how the balance between virus clearance and immune exhaustion may be disrupted when vaccination generates intermediate numbers of specific CD8 T cells. Surprisingly, our model suggests that this adverse effect of vaccination is largely unaffected by the generation of mutant viruses that evade T cell recognition and cannot be avoided by simply increasing the quality (affinity) or diversity of the T cell response. These findings should be taken into account when developing vaccines against persistent infections.     

T-cell vaccination alters the course of murine herpesvirus 68 infection and the establishment of viral latency in mice

Diseases caused by gammaherpesviruses such as Epstein-Barr virus are a major health concern, and there is significant interest in developing vaccines against this class of viral infections. However, the requirements for effective control of gammaherpesvirus infection are only poorly understood. The recent development of the murine herpesvirus MHV-68 model provides an experimental tool to dissect the immune response to gammaherpesvirus infections. In this study, we investigated the impact of priming T cells specific for class I- and class II-restricted epitopes on the acute phase of the infection and the subsequent establishment of latency and infectious mononucleosis. The data show that vaccination with either major histocompatibility complex class I- or class II-restricted T-cell epitopes derived from lytic cycle proteins significantly reduced lung viral titers during the acute infection. Moreover, the peak level of latently infected spleen cells was significantly reduced following vaccination with immunodominant CD8(+) T-cell epitopes. However, this vaccination approach did not prevent the long-term establishment of latency or the development of the infectious mononucleosis-like syndrome in infected mice. Thus, the virus is able to establish latency efficiently despite strong immunological control of the lytic infection.     

Hold everything! Holding policies for protecting plasma supplies

In spite of advances in testing technologies for detecting infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), occasionally blood or plasma is collected that is potentially infectious, but is not detected as such by existing screening tests. We consider the effect of a holding policy for further reducing the number of potentially infectious units that are released for fractionation. The policy dictates a holding period during which all donated units are stored. If a donor tests positive for the infection in question at a subsequent donation, then all of that donor's units currently in storage are discarded. Otherwise, donated units are released at the end of the holding period. In the case of a single disease, we determine optimal holding periods as well as policies that are as effective as the best screening tests currently available.     

口服轮状病毒活疫苗安全性和免疫原性观察

为了观察口服轮状病毒活疫苗在儿童服用后的安全性和免疫原性效果。于惠州市选择63名6月龄~3岁的儿童为观察对象。所用疫苗由兰州生物制品研究所生产,服苗前和服苗后4~5周采末梢血,以中和试验检测抗轮状病毒(G1、G2、G3、G4)型抗体及疫苗株(LLR型)的抗体水平。63名儿童服苗前、后采集的血清样本双份配对均有效者为37人。37人服苗后各型抗体阳转率为47.06%~72.72%;≥4倍增长率为43.40%~66.04%;各型中和抗体免疫前后平均增长2.67~3.01倍。63名服苗儿童中的不良反应为低热3例(24.67%)、中热1例(1.59%)、无高热反应。观察结果表明,轮状病毒具有良好的免疫原性和安全性。     

A Modeling Approach to Investigate Epizootic Outbreaks and Enzootic Maintenance of Rift Valley Fever Virus

We propose a mathematical model to investigate the transmission dynamics of Rift Valley fever (RVF) virus among ruminants. Our findings indicate that in endemic areas RVF virus maintains at a very low level among ruminants after outbreaks and subsequent outbreaks may occur when new susceptible ruminants are recruited into endemic areas or abundant numbers of mosquitoes emerge when herd immunity decreases. Many factors have been shown to have impacts on the severity of RVF outbreaks; a higher probability of death due to RVF among ruminants, a higher mosquito:ruminant ratio, or a shorter lifespan of animals can amplify the magnitude of the outbreaks; vaccination helps to reduce the magnitude of RVF outbreaks and the loss of animals efficiently, and the maximum vaccination effort (a high vaccination rate and a larger number of vaccinated animals) is recommended before the commencement of an outbreak but can be reduced later during the enzootic.     

Cost-effectiveness and budget impact analyses of dengue vaccination in Indonesia

Despite the fact that the incidence and mortality rates due to dengue virus (DENV) infection in Indonesia are relatively high, dengue vaccination has not yet been introduced. This study aimed to analyse the cost-effectiveness and the budget impact of dengue vaccination in Indonesia by taking the potential of pre-vaccination screening into account. An age-structured decision tree model was developed to assess the cost-effectiveness value by applying a single cohort of 4,710,100 children that was followed-up in a 10-year time horizon within a 1-year analytical cycle. The budget impact was analysed in a 5-year period (2020–2024) by considering provinces’ readiness to introduce dengue vaccine and their incidence rate of DENV infection in the last 10 years. Vaccination that was coupled with pre-vaccination screening would reduce dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) by 188,142, 148,089 and 426 cases, respectively. It would save treatment cost at $23,433,695 and $14,091,642 from the healthcare and payer perspective, respectively. The incremental cost-effectiveness ratios (ICERs) would be $5,733 and $5,791 per quality-adjusted-life-year (QALY) gained from both perspectives. The most influential parameters affecting the ICERs were probability of DENV infection, vaccine efficacy, under-reporting factor, vaccine price, case fatality rate and screening cost. It can be concluded that dengue vaccination and pre-vaccination screening would be cost-effective to be implemented in Indonesia. Nevertheless, it seems unaffordable to be implemented since the total required cost for the nationwide vaccination would be 94.44% of routine immunization budget.