Showing papers on "Vaccination published in 2006"

Regulatory T cells, tumour immunity and immunotherapy

Abstract: Tumours express a range of antigens, including self-antigens. Regulatory T cells are crucial for maintaining T-cell tolerance to self-antigens. Regulatory T cells are thought to dampen T-cell immunity to tumour-associated antigens and to be the main obstacle tempering successful immunotherapy and active vaccination. In this Review, I consider the nature and characteristics of regulatory T cells in the tumour microenvironment and their potential multiple suppressive mechanisms. Strategies for therapeutic targeting of regulatory T cells and the effect of regulatory T cells on current immunotherapeutic and vaccine regimens are discussed.

General recommendations on immunization; recommendations of the Advisory Committee on Immunization Practices (ACIP)

Abstract: This report is a revision of General Recommendations on Immunization and updates the 2002 statement by the Advisory Committee on Immunization Practices (ACIP) (CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices and the American Academy of Family Physicians. MMWR 2002;51[No. RR-2]). This report is intended to serve as a general reference on vaccines and immunization. The principal changes include 1) expansion of the discussion of vaccination spacing and timing; 2) an increased emphasis on the importance of injection technique/age/body mass in determining appropriate needle length; 3) expansion of the discussion of storage and handling of vaccines, with a table defining the appropriate storage temperature range for inactivated and live vaccines; 4) expansion of the discussion of altered immunocompetence, including new recommendations about use of live-attenuated vaccines with therapeutic monoclonal antibodies; and 5) minor changes to the recommendations about vaccination during pregnancy and vaccination of internationally adopted children, in accordance with new ACIP vaccine-specific recommendations for use of inactivated influenza vaccine and hepatitis B vaccine. The most recent ACIP recommendations for each specific vaccine should be consulted for comprehensive discussion. This report, ACIP recommendations for each vaccine, and other information about vaccination can be accessed at CDC's National Center for Immunization and Respiratory Diseases (proposed) (formerly known as the National Immunization Program) website at http//:www.cdc.gov/nip.

A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults.

Abstract: Hepatitis B vaccination is the most effective measure to prevent hepatitis B virus (HBV) infection and its consequences, including cirrhosis of the liver, liver cancer, liver failure, and death. In adults, ongoing HBV transmission occurs primarily among unvaccinated persons with behavioral risks for HBV transmission (e.g., heterosexuals with multiple sex partners, injection-drug users [IDUs], and men who have sex with men [MSM]) and among household contacts and sex partners of persons with chronic HBV infection. This report, the second of a two-part statement from the Advisory Committee on Immunization Practices (ACIP), provides updated recommendations to increase hepatitis B vaccination of adults at risk for HBV infection. The first part of the ACIP statement, which provided recommendations for immunization of infants, children, and adolescents, was published previously (CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP]. Part 1: immunization of infants, children, and adolescents. MMWR 2005;54[No. RR-16]:1-33). In settings in which a high proportion of adults have risks for HBV infection (e.g., sexually transmitted disease/human immunodeficiency virus testing and treatment facilities, drug-abuse treatment and prevention settings, health-care settings targeting services to IDUs, health-care settings targeting services to MSM, and correctional facilities), ACIP recommends universal hepatitis B vaccination for all unvaccinated adults. In other primary care and specialty medical settings in which adults at risk for HBV infection receive care, health-care providers should inform all patients about the health benefits of vaccination, including risks for HBV infection and persons for whom vaccination is recommended, and vaccinate adults who report risks for HBV infection and any adults requesting protection from HBV infection. To promote vaccination in all settings, health-care providers should implement standing orders to identify adults recommended for hepatitis B vaccination and administer vaccination as part of routine clinical services, not require acknowledgment of an HBV infection risk factor for adults to receive vaccine, and use available reimbursement mechanisms to remove financial barriers to hepatitis B vaccination.

Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP).

Abstract: Routine vaccination of children is an effective way to reduce hepatitis A incidence in the United States. Since licensure of hepatitis A vaccine during 1995-1996, the hepatitis A childhood immunization strategy has been implemented incrementally, starting with the recommendation of the Advisory Committee on Immunization Practices (ACIP) in 1996 to vaccinate children living in communities with the highest disease rates and continuing in 1999 with ACIP's recommendations for vaccination of children living in states, counties, and communities with consistently elevated hepatitis A rates. These updated recommendations represent the final step in the childhood hepatitis A immunization strategy, routine hepatitis A vaccination of children nationwide. Implementation of these recommendations will reinforce existing vaccination programs, extend the benefits associated with hepatitis A vaccination to the rest of the country, and create the foundation for eventual consideration of elimination of indigenous hepatitis A virus transmission. This report updates ACIP's 1999 recommendations concerning the prevention of hepatitis A through immunization (CDC. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1999:48[No. RR-12]:1-37) and includes 1) new data on the epidemiology of hepatitis A in the era of hepatitis A vaccination of children in selected U.S. areas, 2) results of analyses of the economics of nationwide routine vaccination of children, and 3) recommendations for the routine vaccination of children in the United States. Previous recommendations for vaccination of persons in groups at increased risk for hepatitis A or its adverse consequences and recommendations regarding the use of immune globulin for protection against hepatitis A are unchanged from the 1999 recommendations.

Hepatitis B Virus Infection: Epidemiology and Vaccination

Abstract: Worldwide, two billion people have been infected with hepatitis B virus (HBV), 360 million have chronic infection, and 600,000 die each year from HBV-related liver disease or hepatocellular carcinoma. This comprehensive review of hepatitis B epidemiology and vaccines focuses on definitive and influential studies and highlights current trends, policies, and directions. HBV can be transmitted vertically, through sexual or household contact, or by unsafe injections, but chronic infections acquired during infancy or childhood account for a disproportionately large share of worldwide morbidity and mortality. Vaccination against HBV infection can be started at birth and provides long-term protection against infection in more than 90% of healthy people. In the 1990s, many industrialized countries and a few less-developed countries implemented universal hepatitis B immunization and experienced measurable reductions in HBV-related disease. For example, in Taiwan, the prevalence of chronic infection in children declined by more than 90%. Many resource-poor nations have recently initiated universal hepatitis B immunization programs with assistance from the Global Alliance for Vaccines and Immunization. Further progress towards the elimination of HBV transmission will require sustainable vaccination programs with improved vaccination coverage, practical methods of measuring the impact of vaccination programs, and targeted vaccination efforts for communities at high risk of infection.

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up

Abstract: Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16–23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrolment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy=100%; 95% CI:12–100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.

Randomized, Double‐Blind, Placebo‐Controlled Efficacy Trial of a Bivalent Recombinant Glycoprotein 120 HIV‐1 Vaccine among Injection Drug Users in Bangkok, Thailand

Abstract: In Thailand phase 1/2 trials of monovalent subtype B and bivalent subtype B/E (CRF01_AE) recombinant glycoprotein 120 human immunodeficiency virus type 1 (HIV-1) vaccines were successfully conducted from 1995 to 1998 prompting the first HIV-1 vaccine efficacy trial in Asia. This randomized double-blind placebo-controlled efficacy trial of AIDSVAX B/E (VaxGen) which included 36-months of follow-up was conducted among injection drug users (IDUs) in Bangkok Thailand. The primary end point was HIV-1 infection; secondary end points included plasma HIV-1 load CD4 cell count onset of acquired immunodeficiency syndrome-defining conditions and initiation of antiretroviral therapy. A total of 2546 IDUs were enrolled between March 1999 and August 2000; the median age was 26 years and 93.4% were men. The overall HIV-1 incidence was 3.4 infections/100 person-years (95% confidence interval [CI] 3.0-3.9 infections/100 person-years) and the cumulative incidence was 8.4%. There were no differences between the vaccine and placebo arms. HIV-1 subtype E (83 vaccine and 81 placebo recipients) accounted for 77% of infections. Vaccine efficacy was estimated at 0.1% (95% CI -30.8% to 23.8%; P = .99 log-rank test). No statistically significant effects of the vaccine on secondary end points were observed. Despite the successful completion of this efficacy trial the vaccine did not prevent HIV-1 infection or delay HIV-1 disease progression. (authors)

Safety and Immunogenicity of an Inactivated Subvirion Influenza A (H5N1) Vaccine

Abstract: Background Influenza A (H5N1) viruses could cause a severe worldwide epidemic, with high attack rates, large numbers of deaths and hospitalizations, and wide disruption. Effective vaccines against these viruses in humans are urgently needed. Methods We conducted a multicenter, double-blind two-stage study involving 451 healthy adults 18 to 64 years of age who were randomly assigned in a 2:2:2:2:1 ratio to receive two intramuscular doses of a subvirion influenza A (H5N1) vaccine of 90, 45, 15, or 7.5 μg of hemagglutinin antigen or placebo. The subjects were followed for the safety analysis for 56 days. Serum samples obtained before each vaccination and again 28 days after the second vaccination were tested for H5 antibody by microneutralization and hemagglutination inhibition. Results Mild pain at the injection site was the most common adverse event for all doses of vaccine. The frequency of a serum antibody response was highest among subjects receiving doses of 45 μg or 90 μg. Among those who received two...

T Cell Responses Are Better Correlates of Vaccine Protection in the Elderly

Abstract: It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination. This study prospectively evaluated the relationship between the development of influenza illness, and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure (CHF). Adults age 60 years and older (90 subjects), and 10 healthy young adult controls received the 2003-04 trivalent inactivated influenza vaccine. Laboratory diagnosed influenza (LDI) was documented in 9 of 90 older adults. Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness (LDI subjects) and those who would not (non-LDI subjects). In contrast, PBMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects. The mean IFN-γ:IL-10 ratio in influenza A/H3N2-stimulated PBMC was 10-fold lower in LDI vs non-LDI subjects. Pre-and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI. In non-CHF subjects with LDI, granzyme B levels increased to high levels at the time of influenza infection. In conclusion, measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people. Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults.

Factors That Are Associated With Parental Acceptance of Human Papillomavirus Vaccines: A Randomized Intervention Study of Written Information About HPV

Abstract: OBJECTIVES. Prophylactic vaccines against human papillomavirus (HPV) are expected to be available for public use by 2007 and likely will be targeted to preadolescent children. Parental acceptance of these vaccines will be critical for their success. The objectives of this study were (1) to determine the overall acceptance of HPV vaccines for preadolescent children by parents, (2) to evaluate the influence of written educational information about HPV on parental acceptability of HPV vaccines, and (3) to identify independent predictors associated with HPV vaccine acceptability by parents. METHODS. A randomized intervention study within a cross-sectional survey was conducted. Parental HPV vaccine acceptability was measured under 3 different hypothetical scenarios. A self-administered survey on the knowledge, attitudes, and beliefs about HPV and HPV vaccines was sent to 1600 parents of 8- to 12-year-old children. In addition to a baseline paragraph about HPV that was received by all study participants, a random half of the study participants received a detailed “HPV Information Sheet” outlining the epidemiology and potential clinical sequelae of HPV infection. Independent predictors of parental HPV vaccine acceptability were determined using multivariate linear regression models. RESULTS. Parents who received the HPV information sheet had higher mean scores on the HPV knowledge assessment tool than the control group. However, despite this apparent improvement in knowledge, there was not a statistically significant difference in HPV vaccine acceptability between the 2 groups. CONCLUSIONS. Providing parents with an HPV information sheet did seem to improve knowledge about HPV, but this increased knowledge had little effect on the acceptability of these vaccines by parents for their children. Instead, attitudes and life experiences seemed to be more important factors influencing HPV vaccine acceptability among parents.

Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP).

Abstract: During spring 2005, two tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) products formulated for use in adolescents (and, for one product, use in adults) were licensed in the United States (BOOSTRIX, GlaxoSmithKline Biologicals, Rixensart, Belgium [licensed May 3, 2005, for use in persons aged 10-18 years], and ADACEL, sanofi pasteur, Toronto, Ontario, Canada [licensed June 10, 2005, for use in persons aged 11-64 years]). Prelicensure studies demonstrated safety and efficacy against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adolescents. To reduce pertussis morbidity in adolescents and maintain the standard of care for tetanus and diphtheria protection, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adolescents aged 11-18 years should receive a single dose of Tdap instead of tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they have completed the recommended childhood diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP)/ diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series (five doses of pediatric DTP/DTaP before the seventh birthday; if the fourth dose was administered on or after the fourth birthday, the fifth dose is not needed) and have not received Td or Tdap. The preferred age for Tdap vaccination is 11-12 years; 2) adolescents aged 11-18 years who received Td, but not Tdap, are encouraged to receive a single dose of Tdap to provide protection against pertussis if they have completed the recommended childhood DTP/DTaP vaccination series. An interval of at least 5 years between Td and Tdap is encouraged to reduce the risk for local and systemic reactions after Tdap vaccination. However, an interval less than 5 years between Td and Tdap can be used; and 3) vaccine providers should administer Tdap and tetravalent meningococcal conjugate vaccine (Menactra, sanofi pasteur, Swiftwater, Pennsylvania) to adolescents aged 11-18 years during the same visit if both vaccines are indicated and available. This statement 1) reviews tetanus, diphtheria and pertussis vaccination policy in the United States, with emphasis on adolescents; 2) describes the clinical features and epidemiology of pertussis among adolescents; 3) summarizes the immunogenicity, efficacy, and safety data of the two Tdap vaccines licensed for use among adolescents; and 4) presents recommendations for tetanus, diphtheria, and pertussis vaccination among adolescents aged 11-18 years.

Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women.

Abstract: OBJECTIVE. Prophylactic vaccination of 16- to 23-year-old females with a quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine has been shown to prevent type-specific human papillomavirus infection and associated clinical disease. We conducted a noninferiority immunogenicity study to bridge the efficacy findings in young women to preadolescent and adolescent girls and boys, who represent a primary target for human papillomavirus vaccination. METHODS. We enrolled 506 girls and 510 boys (10–15 years of age) and 513 females (16–23 years of age). Participants were vaccinated on day 1, at month 2, and at month 6, and serology testing was performed on day 1 and at months 3 and 7 on blinded samples. Neutralizing antibody concentrations were determined using type-specific immunoassays and summarized as geometric mean titers and seroconversion rates. Vaccine tolerability also was assessed. RESULTS. By month 7, seroconversion rates were ≥99% for all 4 human papillomavirus types in each group. By month 7, compared with women, anti–human papilloma virus geometric mean titers in girls or boys were noninferior and were 1.7- to 2.7-fold higher. Most (>97%) injection-site adverse events were mild to moderate in intensity. Significantly more boys (13.8%) and girls (12.8%) than women (7.3%) reported fevers ≥37.8°C within 5 days of vaccination. Most (96.4%) fevers were mild ( CONCLUSIONS. Noninferior immunogenic responses to all 4 human papillomavirus types in the quadrivalent vaccine permit the bridging of efficacy data that were generated in young women to girls. The results in boys lend support for the implementation of gender-neutral human papillomavirus vaccination programs. This vaccine generally was well tolerated.

Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer

Abstract: Purpose: The initial goal of this study was to test the immunologic and clinical effects of a new cancer vaccine consisting of dendritic cells (DC) transduced with the full-length wild-type p53 gene delivered via an adenoviral vector in patients with extensive stage small cell lung cancer. Experimental Design: Twenty-nine patients with extensive stage small cell lung cancer were vaccinated repeatedly at 2-week intervals. Most of the patients received three immunizations. p53-specific responses were evaluated, and phenotype and function of T cells, DCs, and immature myeloid cells were analyzed and correlated with antigen-specific immune responses. Objective clinical response to vaccination as well as subsequent chemotherapy was evaluated. Results: p53-specific T cell responses to vaccination were observed in 57.1% of patients. Immunologic responses to vaccination were positively associated with a moderate increase in the titer of antiadenovirus antibodies, and negatively with an accumulation of immature myeloid cells. One patient showed a clinical response to vaccination whereas most of the patients had disease progression. However, we observed a high rate of objective clinical responses to chemotherapy (61.9%) that immediately followed vaccination. Clinical response to subsequent chemotherapy was closely associated with induction of immunologic response to vaccination. Conclusions: This study provides clinical support for an emerging paradigm in cancer immunotherapy, wherein optimal use of vaccination might be more effective, not as a separate modality, but in direct combination with chemotherapy.

Influenza vaccine for patients with chronic obstructive pulmonary disease

Abstract: Background: Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in COPD patients but there is also the potential for influenza vaccination to cause adverse effects or not to be cost effective. Objectives: To evaluate the evidence from RCTs for a treatment effect of influenza vaccination in COPD subjects. Outcomes of interest were exacerbation rates, hospitalisations, mortality, lung function and adverse effects. Search strategy: We searched the Cochrane Airways Group Specialised Register of trials, and reference lists of articles. References were also provided by a number of drug companies we contacted. The latest search was carried out in May 2009. Selection criteria: RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine in persons with COPD. Studies of people with asthma were excluded. Data collection and analysis: Two reviewers extracted data. All entries were double checked. Study authors and drug companies were contacted for missing information. Main results: Eleven trials were included but only six of these were specifically performed in COPD patients. The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Inactivated vaccine in COPD patients resulted in a significant reduction in the total number of exacerbations per vaccinated subject compared with those who received placebo (weighted mean difference (WMD) -0.37, 95% confidence interval -0.64 to -0.11, P = 0.006). This was due to the reduction in "late" exacerbations occurring after three or four weeks (WMD -0.39, 95% CI -0.61 to -0.18, P = 0.0004). In Howells 1961, the number of patients experiencing late exacerbations was also significantly less (odds ratio 0.13, 95% CI 0.04 to 0.45, P = 0.002). Both Howells 1961 and Wongsurakiat 2004 found that inactivated influenza vaccination reduced influenza -related respiratory infections (WMD 0.19, 95% CI 0.07 to 0.48, P = 0.0005). In both COPD patient and in elderly patients (only a minority of whom had COPD), there was a significant increase in the occurrence of local adverse reactions in vaccinees, but the effects were generally mild and transient. There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination. The studies are too small to have detected any effect on mortality. An updated search conducted in September 2001 did not yield any further studies. A search in 2003 yielded two further reports of the same eligible study Gorse 2003. A search in 2004 yielded two reports of the another eligible study Wongsurakiat 2004. The author informed us of another report of the same study Wongsurakiat 2004/2. An update search inMay 2006 did not identify any new studies for consideration. Authors' conclusions: It appears, from the limited number of studies performed, that inactivated vaccine reduces exacerbations in COPD patients. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There is a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis

Abstract: Objective To evaluate the effects of hepatitis B vaccine and immunoglobulin in newborn infants of mothers positive for hepatitis B surface antigen. Design Systematic review and meta-analysis of randomised clinical trials. Data sources Electronic databases and hand searches. Review methods Randomised clinical trials were assessed for methodological quality. Meta-analysis was undertaken on three outcomes: the relative risks of hepatitis B occurrence, antibody levels to hepatitis B surface antigen, and adverse events. Results 29 randomised clinical trials were identified, five of which were considered high quality. Only three trials reported inclusion of mothers negative for hepatitis B e antigen. Compared with placebo or no intervention, vaccination reduced the occurrence of hepatitis B (relative risk 0.28, 95% confidence interval 0.20 to 0.40; four trials). No significant difference in hepatitis B occurrence was found between recombinant vaccine and plasma derived vaccine (1.00, 0.71 to 1.42; four trials) and between high dose versus low dose vaccine (plasma derived vaccine 0.97, 0.55 to 1.68, three trials; recombinant vaccine 0.78, 0.31 to 1.94, one trial). Compared with placebo or no intervention, hepatitis B immunoglobulin or the combination of plasma derived vaccine and hepatitis B immunoglobulin reduced hepatitis B occurrence (immunoglobulin 0.50, 0.41 to 0.60, one trial; vaccine and immunoglobulin 0.08, 0.03 to 0.17, three trials). Compared with vaccine alone, vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (0.54, 0.41 to 0.73; 10 trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem safe, but few trials reported adverse events. Conclusion Hepatitis B vaccine, hepatitis B immunoglobulin, and vaccine plus immunoglobulin prevent hepatitis B occurrence in newborn infants of mothers positive for hepatitis B surface antigen.

Influenza vaccination of healthcare workers: a literature review of attitudes and beliefs.

Abstract: Influenza vaccination coverage among healthcare workers (HCW) is insufficient despite health authority recommendations in many countries. Numerous vaccination campaigns encouraging HCW to be vaccinated have met with resistance. We reviewed published influenza vaccination programs in healthcare settings to understand the reasons for their success and failure, as well as the attitudes and beliefs of HCW. Relevant articles published up to June 2004 were identified in the MEDLINE/Pubmed database. Thirty-two studies performed between 1985 and 2002 reported vaccination rates of 2.1–82%. Vaccination campaigns including easy access to free vaccine and an educational program tended to obtain the highest uptake, particularly in the USA. Yet, even this type of campaign was not always successful. Two main barriers to satisfactory vaccine uptake were consistently reported: (1) misperception of influenza, its risks, the role of HCW in its transmission to patients, and the importance and risks of vaccination (2) lack of (or perceived lack of) conveniently available vaccine. To overcome these barriers and increase uptake, vaccination campaigns must be carefully designed and implemented taking account of the specific needs at each healthcare institution.

Association Between Health Care Providers' Influence on Parents Who Have Concerns About Vaccine Safety and Vaccination Coverage

Abstract: OBJECTIVES. Parents who have concerns about vaccine safety may be reluctant to have their children vaccinated. The purpose of this study was to explore how vaccination coverage among children 19 to 35 months of age is associated with health care providers9 influence on parents9 decision to vaccinate their children, and with parents9 beliefs about vaccine safety. METHODS. Parents of 7695 children 19 to 35 months of age sampled by the National Immunization Survey were administered the National Immunization Survey Parental Knowledge Module between the third quarter of 2001 and the fourth quarter of 2002. Health care providers were defined as a physician, nurse, or any other type of health care professional. Parents provided responses that summarized the degree to which they believed vaccines were safe, and the influence providers had on their decisions to vaccinate their children. Children were determined to be up-to-date if their vaccination providers reported administering ≥4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine, ≥3 doses of polio vaccine, ≥1 dose of measles-mumps-rubella vaccine, ≥3 doses of Haemophilus influenzae type b vaccine, and ≥3 doses of hepatitis B vaccine. RESULTS. Of all of the parents, 5.7% thought that vaccines were not safe, and 21.5% said that their decision to vaccinate their children was not influenced by a health care provider. Compared with parents who responded that providers were not influential in their decision to vaccinate their children, parents who responded that providers were influential were twice as likely to respond that vaccines were safe for children. Among children whose parents believed that vaccines were not safe, those whose parents9 decision to vaccinate was influenced by a health care provider had an estimated vaccination coverage rate that was significantly higher than the estimated coverage rate among children whose parents9 decision was not influenced by a health care provider (74.4% vs 50.3%; estimated difference: 24.1%). CONCLUSIONS. Health care providers have a positive influence on parents to vaccinate their children, including parents who believe that vaccinations are unsafe. Physicians, nurses, and other health care professionals should increase their efforts to build honest and respectful relationships with parents, especially when parents express concerns about vaccine safety or have misconceptions about the benefits and risks of vaccinations.

Phase 1 Safety and Immunogenicity Evaluation of a Multiclade HIV‐1 Candidate Vaccine Delivered by a Replication‐Defective Recombinant Adenovirus Vector

Abstract: More than 40 million people are living with HIV/AIDS. Three million deaths occur annually because of HIV/ AIDS, with ∼5 million new infections occurring in 2005 [1]. Development of an effective vaccine would be an important intervention to help control the expanding global pandemic. Adenovirus serotype 5 (Ad5) has been developed as a replication-defective recombinant vector (rAd5) to deliver intracellular genes via a number of routes [2]. Vaccination with rAd5 results in transient intracellular gene expression followed by rapid clearance [3]. Cellular and humoral immune responses have been induced in preclinical studies of rAd5 vaccines for HIV-1, simian immunodeficiency virus (SIV), and simian-human immunodeficiency virus (SHIV) [4–7]. This approach builds on previous successes with other infectious disease models, particularly for Ebola virus, against which nonhuman primates have been protected from lethal challenge [8, 9]. Recently, immunization of chimpanzees with rAd expressing hepatitis C virus (HCV) nonstructural genes resulted in T cell–mediated protection against heterologous HCV challenge [10]. These preclinical studies support the concept that gene-based vaccination can induce effective immunity against viral infections in primates. The development of an HIV vaccine that is effective against multiple circulating viral clades remains a scientific priority and urgent public health need [11]. The rAd5 vaccine evaluated in the present clinical trial was designed to express an HIV-1 clade B Gag-Pol fusion protein and Env glycoproteins from HIV-1 clades A, B, and C. Here, we report the findings from the first phase 1 clinical trial of this multigene, multiclade rAd5 HIV-1 candidate vaccine.

Epidemiology of HPV 16 and Cervical Cancer in Finland and the Potential Impact of Vaccination: Mathematical Modelling Analyses

Abstract: Background Candidate human papillomavirus (HPV) vaccines have demonstrated almost 90%-100% efficacy in preventing persistent, type-specific HPV infection over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention of precancerous lesions in phase III clinical trials, they will be licensed for public use in the near future. How these vaccines will be used in countries with national cervical cancer screening programmes is an important question. Methods and Findings We developed a transmission model of HPV 16 infection and progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence over time. The model was used to estimate the transmission probability of the virus, to look at the effect of changes in patterns of sexual behaviour and smoking on age-specific trends in cancer incidence, and to explore the impact of HPV 16 vaccination. We estimated a high per-partnership transmission probability of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour and smoking accounted, in part, for the increase seen in cervical cancer incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in opportunistic immunisation) and high (90% in a national immunisation programme) coverage of the adolescent population, vaccinating women and men had little benefit over vaccinating women alone. We estimate that vaccinating 90% of young women before sexual debut has the potential to decrease HPV type-specific (e.g., type 16) cervical cancer incidence by 91%. If older women are more likely to have persistent infections and progress to cancer, then vaccination with a duration of protection of less than 15 y could result in an older susceptible cohort and no decrease in cancer incidence. While vaccination has the potential to significantly reduce type-specific cancer incidence, its combination with screening further improves cancer prevention. Conclusions HPV vaccination has the potential to significantly decrease HPV type-specific cervical cancer incidence. High vaccine coverage of women alone, sustained over many decades, with a long duration of vaccine-conferred protection, would have the greatest impact on type-specific cancer incidence. This level of coverage could be achieved through national coordinated programmes, with surveillance to detect cancers caused by nonvaccine oncogenic HPV types.

Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: an experiment of nature.

Abstract: During a pandemic, influenza vaccines that rely on neutralizing antibodies to protect against matched viruses might not be available early enough. Much broader (heterosubtypic) immune protection is seen in animals. Do humans also have cross-subtype immunity? To investigate this issue, archival records from the Cleveland Family Study, which was conducted before and during the 1957 pandemic (during which a shift from subtype H1N1 to H2N2 occurred), were analyzed. Only 5.6% of the adults who had had symptomatic influenza A in earlier study years developed influenza during the pandemic, despite living in households with participants who had influenza. In contrast, 55.2% of the children who had had symptomatic influenza A contracted it again. These findings suggest an impact of accumulated heterosubtypic immunity during a pandemic. Such immunity, as well as its implications for vaccination, should be further investigated.

Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines.

Abstract: The patterns of cellular immune responses induced by live attenuated influenza vaccine (LAIV) versus those of the trivalent inactivated influenza vaccine (TIV) have not been studied extensively, especially in children. The goals of this study were to evaluate the effects of TIV and LAIV immunization on cellular immunity to live influenza A virus in children and adults and to explore factors associated with variations in responses to influenza vaccines among individuals. A gamma interferon (IFN-γ) flow cytometry assay was used to measure IFN-γ-producing (IFN-γ+) NK and T cells in peripheral blood mononuclear cell cultures stimulated with a live influenza A virus strain before and after LAIV or TIV immunization of children and adults. The mean percentages of influenza A virus-specific IFN-γ+ CD4 and CD8 T cells increased significantly after LAIV, but not TIV, immunization in children aged 5 to 9 years. No increases in the mean levels of influenza A virus-reactive IFN-γ+ T cells and NK cells were observed in adults given LAIV or TIV. TIV induced a significant increase in influenza A virus-reactive T cells in 6-month- to 4-year-old children; LAIV was not evaluated in this age group. The postvaccination changes (n-fold) in the percentages of influenza A virus-reactive IFN-γ+ T and NK cells in adults were highly variable and correlated inversely with the prevaccination percentages, in particular with that of the CD56dim NK cell subset. In conclusion, our findings identify age, type of vaccine, and prevaccination levels of immune reactivity to influenza A virus as factors significantly associated with the magnitude of cellular immune responses to influenza vaccines.

Advances in tuberculosis vaccine strategies.

Abstract: Tuberculosis (TB), an ancient human scourge, is a growing health problem in the developing world. Approximately two million deaths each year are caused by TB, which is the leading cause of death in HIV-infected individuals. Clearly, an improved TB vaccine is desperately needed. Heterologous prime-boost regimens probably represent the best hope for an improved vaccine regimen to prevent TB. This first generation of new vaccines might also complement drug treatment regimens and be effective against reactivation of TB from the latent state, which would significantly enhance their usefulness.

Protection of mice and poultry from lethal H5N1 avian influenza virus through adenovirus-based immunization

Abstract: The recent emergence of highly pathogenic avian influenza virus (HPAI) strains in poultry and their subsequent transmission to humans in Southeast Asia have raised concerns about the potential pandemic spread of lethal disease. In this paper we describe the development and testing of an adenovirus-based influenza A virus vaccine directed against the hemagglutinin (HA) protein of the A/Vietnam/1203/2004 (H5N1) (VN/1203/04) strain isolated during the lethal human outbreak in Vietnam from 2003 to 2005. We expressed different portions of HA from a recombinant replication-incompetent adenoviral vector, achieving vaccine production within 36 days of acquiring the virus sequence. BALB/c mice were immunized with a prime-boost vaccine and exposed to a lethal intranasal dose of VN/1203/04 H5N1 virus 70 days later. Vaccination induced both HA-specific antibodies and cellular immunity likely to provide heterotypic immunity. Mice vaccinated with full-length HA were fully protected from challenge with VN/1203/04. We next evaluated the efficacy of adenovirus-based vaccination in domestic chickens, given the critical role of fowl species in the spread of HPAI worldwide. A single subcutaneous immunization completely protected chickens from an intranasal challenge 21 days later with VN/1203/04, which proved lethal to all control-vaccinated chickens within 2 days. These data indicate that the rapid production and subsequent administration of recombinant adenovirus-based vaccines to both birds and high-risk individuals in the face of an outbreak may serve to control the pandemic spread of lethal avian influenza.