Showing papers on "Vaccination published in 2014"
TL;DR: The results show a variety of factors as being associated with vaccine hesitancy but they do not allow for a complete classification and confirmation of their independent and relative strength of influence.
1,416 citations
TL;DR: Developing new therapies that can improve HBsAg clearance and virological cure is warranted because long-term antiviral treatment can reverse cirrhosis and reduce hepatocellular carcinoma.
1,137 citations
TL;DR: Refuting claims of an MMR/autism link successfully reduced misperceptions that vaccines cause autism but nonetheless decreased intent to vaccinate among parents who had the least favorable vaccine attitudes.
Abstract: OBJECTIVES: To test the effectiveness of messages designed to reduce vaccine misperceptions and increase vaccination rates for measles-mumps-rubella (MMR). METHODS: A Web-based nationally representative 2-wave survey experiment was conducted with 1759 parents age 18 years and older residing in the United States who have children in their household age 17 years or younger (conducted June–July 2011). Parents were randomly assigned to receive 1 of 4 interventions: (1) information explaining the lack of evidence that MMR causes autism from the Centers for Disease Control and Prevention; (2) textual information about the dangers of the diseases prevented by MMR from the Vaccine Information Statement; (3) images of children who have diseases prevented by the MMR vaccine; (4) a dramatic narrative about an infant who almost died of measles from a Centers for Disease Control and Prevention fact sheet; or to a control group. RESULTS: None of the interventions increased parental intent to vaccinate a future child. Refuting claims of an MMR/autism link successfully reduced misperceptions that vaccines cause autism but nonetheless decreased intent to vaccinate among parents who had the least favorable vaccine attitudes. In addition, images of sick children increased expressed belief in a vaccine/autism link and a dramatic narrative about an infant in danger increased self-reported belief in serious vaccine side effects. CONCLUSIONS: Current public health communications about vaccines may not be effective. For some parents, they may actually increase misperceptions or reduce vaccination intention. Attempts to increase concerns about communicable diseases or correct false claims about vaccines may be especially likely to be counterproductive. More study of pro-vaccine messaging is needed.
977 citations
TL;DR: This review presents findings from 25 studies comparing inactivated parenteral influenza vaccine against placebo or do-nothing control groups as the most relevant to decision-making over single influenza seasons in North America, South America, and Europe between 1969 and 2009.
Abstract: Background
Different types of influenza vaccines are currently produced worldwide. Healthy adults are presently targeted mainly in North America.
Objectives
Identify, retrieve and assess all studies evaluating the effects of vaccines against influenza in healthy adults.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010, issue 2), MEDLINE (January 1966 to June 2010) and EMBASE (1990 to June 2010).
Selection criteria
Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally-occurring influenza in healthy individuals aged 16 to 65 years. We also included comparative studies assessing serious and rare harms.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data.
Main results
We included 50 reports. Forty (59 sub-studies) were clinical trials of over 70,000 people. Eight were comparative non-RCTs and assessed serious harms. Two were reports of harms which could not be introduced in the data analysis. In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation, 4% of unvaccinated people versus 1% of vaccinated people developed influenza symptoms (risk difference (RD) 3%, 95% confidence interval (CI) 2% to 5%). The corresponding figures for poor vaccine matching were 2% and 1% (RD 1, 95% CI 0% to 3%). These differences were not likely to be due to chance. Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates. Inactivated vaccines caused local harms and an estimated 1.6 additional cases of Guillain-Barre Syndrome per million vaccinations. The harms evidence base is limited.
Authors' conclusions
Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.
WARNING:
This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.
870 citations
TL;DR: The findings show that dengue vaccine is efficacious when given as three injections at months 0, 6, and 12 to children aged 2-14 years in endemic areas in Asia, and has a good safety profile.
812 citations
29 Aug 2014
TL;DR: This report summarizes the epidemiology of human papillomavirus (HPV) and associated diseases, describes the licensed HPV vaccines, provides updated data from clinical trials and postlicensure safety studies, and compiles recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of HPV vaccines.
Abstract: This report summarizes the epidemiology of human papillomavirus (HPV) and associated diseases, describes the licensed HPV vaccines, provides updated data from clinical trials and postlicensure safety studies, and compiles recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of HPV vaccines. Persistent infection with oncogenic HPV types can cause cervical cancer in women as well as other anogenital and oropharyngeal cancers in women and men. HPV also causes genital warts. Two HPV vaccines are licensed in the United States. Both are composed of type-specific HPV L1 protein, the major capsid protein of HPV. Expression of the L1 protein using recombinant DNA technology produces noninfectious virus-like particles (VLPs). Quadrivalent HPV vaccine (HPV4) contains four HPV type-specific VLPs prepared from the L1 proteins of HPV 6, 11, 16, and 18. Bivalent HPV vaccine (HPV2) contains two HPV type-specific VLPs prepared from the L1 proteins of HPV 16 and 18. Both vaccines are administered in a 3-dose series. ACIP recommends routine vaccination with HPV4 or HPV2 for females aged 11 or 12 years and with HPV4 for males aged 11 or 12 years. Vaccination also is recommended for females aged 13 through 26 years and for males aged 13 through 21 years who were not vaccinated previously. Males aged 22 through 26 years may be vaccinated. ACIP recommends vaccination of men who have sex with men and immunocompromised persons (including those with HIV infection) through age 26 years if not previously vaccinated. As a compendium of all current recommendations for use of HPV vaccines, information in this report is intended for use by clinicians, vaccination providers, public health officials, and immunization program personnel as a resource. ACIP recommendations are reviewed periodically and are revised as indicated when new information and data become available.
777 citations
TL;DR: A systematic review of the literature on barriers to HPV vaccination among US adolescents to inform future efforts to increase HPV vaccine coverage was conducted by as mentioned in this paper, where 55 relevant articles were summarized by target populations: health care professionals, parents, underserved and disadvantaged populations, and males.
Abstract: Importance Since licensure of the human papillomavirus (HPV) vaccine in 2006, HPV vaccine coverage among US adolescents has increased but remains low compared with other recommended vaccines. Objective To systematically review the literature on barriers to HPV vaccination among US adolescents to inform future efforts to increase HPV vaccine coverage. Evidence Review We searched PubMed and previous review articles to identify original research articles describing barriers to HPV vaccine initiation and completion among US adolescents. Only articles reporting data collected in 2009 or later were included. Findings from 55 relevant articles were summarized by target populations: health care professionals, parents, underserved and disadvantaged populations, and males. Findings Health care professionals cited financial concerns and parental attitudes and concerns as barriers to providing the HPV vaccine to patients. Parents often reported needing more information before vaccinating their children. Concerns about the vaccine’s effect on sexual behavior, low perceived risk of HPV infection, social influences, irregular preventive care, and vaccine cost were also identified as potential barriers among parents. Some parents of sons reported not vaccinating their sons because of the perceived lack of direct benefit. Parents consistently cited health care professional recommendations as one of the most important factors in their decision to vaccinate their children. Conclusions and Relevance Continued efforts are needed to ensure that health care professionals and parents understand the importance of vaccinating adolescents before they become sexually active. Health care professionals may benefit from guidance on communicating HPV recommendations to patients and parents. Further efforts are also needed to reduce missed opportunities for HPV vaccination when adolescents interface with the health care system. Efforts to increase uptake should take into account the specific needs of subgroups within the population. Efforts that address system-level barriers to vaccination may help to increase overall HPV vaccine uptake.
744 citations
TL;DR: Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should result in a further decline in childhood mortality and development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest.
Abstract: Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO's Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer's disease.
615 citations
TL;DR: Among persons 65 years of age or older, IIV3-HD induced significantly higher antibody responses and provided better protection against laboratory-confirmed influenza illness than did IIV3-SD.
Abstract: BACKGROUND As compared with a standard-dose vaccine, a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza among adults 65 years of age or older. This study evaluated whether IIV3-HD also improves protection against laboratory-confirmed influenza illness. METHODS We conducted a phase IIIb–IV, multicenter, randomized, double-blind, active-controlled trial to compare IIV3-HD (60 μg of hemagglutinin per strain) with standarddose trivalent, inactivated influenza vaccine (IIV3-SD [15 μg of hemagglutinin per strain]) in adults 65 years of age or older. Assessments of relative efficacy, effectiveness, safety (serious adverse events), and immunogenicity (hemagglutinationinhibition [HAI] titers) were performed during the 2011–2012 (year 1) and the 2012–2013 (year 2) northern-hemisphere influenza seasons. RESULTS A total of 31,989 participants were enrolled from 126 research centers in the United States and Canada (15,991 were randomly assigned to receive IIV3-HD, and 15,998 to receive IIV3-SD). In the intention-to-treat analysis, 228 participants in the IIV3HD group (1.4%) and 301 participants in the IIV3-SD group (1.9%) had laboratoryconfirmed influenza caused by any viral type or subtype associated with a protocol-defined influenza-like illness (relative efficacy, 24.2%; 95% confidence interval [CI], 9.7 to 36.5). At least one serious adverse event during the safety surveillance period was reported by 1323 (8.3%) of the participants in the IIV3-HD group, as compared with 1442 (9.0%) of the participants in the IIV3-SD group (relative risk, 0.92; 95% CI, 0.85 to 0.99). After vaccination, HAI titers and seroprotection rates (the percentage of participants with HAI titers ≥1:40) were significantly higher in the IIV3-HD group. CONCLUSIONS Among persons 65 years of age or older, IIV3-HD induced significantly higher antibody responses and provided better protection against laboratory-confirmed influenza illness than did IIV3-SD. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01427309.)
613 citations
TL;DR: The assessment of the programme of pertussis vaccination in pregnancy in England is consistent with high vaccine effectiveness, which probably results from protection of infants by both passive antibodies and reduced maternal exposure, and will provide valuable information to international policy makers.
604 citations
Journal Article•
TL;DR: Assessment of progress with HPV vaccination coverage among adolescents aged 13-17 years, characterize adherence with recommendations for HPV vaccination by the 13th birthday, and describe HPV vaccine adverse reports received postlicensure indicate that HPV4 is safe.
Abstract: Since mid-2006, a licensed human papillomavirus (HPV) vaccine has been available and recommended by the Advisory Committee on Immunization Practices (ACIP) for routine vaccination of adolescent girls at ages 11 or 12 years. Two vaccines that protect against HPV infection are currently available in the United States. Both the quadrivalent (HPV4) and bivalent (HPV2) vaccines protect against HPV types 16 and 18, which cause 70% of cervical cancers; HPV4 also protects against HPV types 6 and 11, which cause 90% of genital warts. In 2011, the ACIP also recommended HPV4 for the routine vaccination of adolescent boys at ages 11 or 12 years. HPV vaccines can be safely co-administered with other routinely recommended vaccines, and ACIP recommends administration of all age-appropriate vaccines during a single visit. To assess progress with HPV vaccination coverage among adolescents aged 13-17 years, characterize adherence with recommendations for HPV vaccination by the 13th birthday, and describe HPV vaccine adverse reports received postlicensure, CDC analyzed data from the 2007-2013 National Immunization Survey-Teen (NIS-Teen) and national postlicensure vaccine safety data among females and males. Vaccination coverage with ≥1 dose of any HPV vaccine increased significantly from 53.8% (2012) to 57.3% (2013) among adolescent girls and from 20.8% (2012) to 34.6% (2013) among adolescent boys. Receipt of ≥1 dose of HPV among girls by age 13 years increased with each birth cohort; however, missed vaccination opportunities were common. Had HPV vaccine been administered to adolescent girls born in 2000 during health care visits when they received another vaccine, vaccination coverage for ≥1 dose by age 13 years for this cohort could have reached 91.3%. Postlicensure monitoring data continue to indicate that HPV4 is safe. Improving practice patterns so that clinicians use every opportunity to recommend HPV vaccines and address questions from parents can help realize reductions in vaccine-preventable infections and cancers caused by HPV.
TL;DR: The ability to engineer OVs that express immune-stimulating 'cargo', the induction of immunogenic tumour cell death by OVs and the selective targeting of OVs to tumour beds suggests that they are the ideal reagents to enhance antitumour immune responses.
Abstract: Recent clinical data have emphatically shown the capacity of our immune systems to eradicate even advanced cancers. Although oncolytic viruses (OVs) were originally designed to function as tumour-lysing therapeutics, they have now been clinically shown to initiate systemic antitumour immune responses. Cell signalling pathways that are activated and promote the growth of tumour cells also favour the growth and replication of viruses within the cancer. The ability to engineer OVs that express immune-stimulating 'cargo', the induction of immunogenic tumour cell death by OVs and the selective targeting of OVs to tumour beds suggests that they are the ideal reagents to enhance antitumour immune responses. Coupling of OV therapy with tumour antigen vaccination, immune checkpoint inhibitors and adoptive cell therapy seems to be ready to converge towards a new generation of multimodal therapeutics to improve outcomes for cancer patients.
TL;DR: The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussedis will require the development of improved vaccines.
Abstract: Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naive animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naive and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.
TL;DR: Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV.
Abstract: Background There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus (HIV) infection and protection of their infants. Methods We conducted two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccine (IIV3) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected. The immunogenicity, safety, and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth. Immune responses were measured with a hemagglutination inhibition (HAI) assay, and influenza was diagnosed by means of reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays of respiratory samples. Results The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV. At 1 month after vaccination, seroconversion rates and the proportion of partic...
TL;DR: BCG induces sustained changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at thelevel of heterologous Th1/Th17 responses 1 year after vaccination.
Abstract: We have recently shown that BCG (Bacillus Calmette-Guerin) vaccination in healthy volunteers induces epigenetic reprogramming of monocytes, leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination. This phenomenon was named 'trained immunity'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months postvaccination, but these effects were less pronounced 1 year after vaccination. However, monocytes recovered 1 year after vaccination had an increased expression of pattern recognition receptors such as CD14, Toll-like receptor 4 (TLR4) and mannose receptor, and this correlated with an increase in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses.
TL;DR: An unappreciated role for gut microbiota in promoting immunity to vaccination is revealed, with TLR5-mediated sensing of the microbiota impacting antibody responses to the inactivated polio vaccine, but not to adjuvanted vaccines or the live-attenuated yellow fever vaccine.
Duke University1, Durham University2, Fred Hutchinson Cancer Research Center3, National Institutes of Health4, University of California, Santa Cruz5, Harvard University6, Thailand Ministry of Public Health7, Mahidol University8, Sanofi Pasteur9, Rutgers University10, New York University11, Walter Reed Army Institute of Research12
TL;DR: HIV-1–specific IgG3 responses were not long-lived, which was consistent with the waning efficacy of the RV144 vaccine, and should be evaluated in future HIV-1 vaccine efficacy trials to further refine immune correlates of protection.
Abstract: HIV-1-specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass profiles between different vaccine regimens used in clinical trials with divergent efficacy outcomes can provide information on the quality of the vaccine-induced B cell response. We show that HIV-1-specific IgG3 distinguished two HIV-1 vaccine efficacy studies (RV144 and VAX003 clinical trials) and correlated with decreased risk of HIV-1 infection in a blinded follow-up case-control study with the RV144 vaccine. HIV-1-specific IgG3 responses were not long-lived, which was consistent with the waning efficacy of the RV144 vaccine. These data suggest that specific vaccine-induced HIV-1 IgG3 should be tested in future studies of immune correlates in HIV-1 vaccine efficacy trials.
TL;DR: Vaccines have a history that started late in the 18th century and from the late 19th century, vaccines could be developed in the laboratory and in the 21st century, molecular biology permits vaccine development that was not possible before.
Abstract: Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.
TL;DR: This review will discuss the use of animal models for vaccine research, clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines based on new mechanistic insight about the inhibitory mechanism of maternal antibodies.
Abstract: Neonates have an immature immune system which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is examplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B-cell receptor (BCR) with the Fcg receptor IIB (FcgRIIB) by a vaccine-antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B-cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2) signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing this concept.
TL;DR: A wide variation in the reported basis for vaccine hesitancy across countries was revealed and it was revealed that context, time, place, place and vaccine specific influences on vaccine Hesitancy are different.
TL;DR: The antibody landscape was introduced, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, and it was found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters.
Abstract: We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
TL;DR: BCG vaccination of healthy volunteers increased proinflammatory cytokine production following ex vivo stimulation of NK cells with mycobacteria and other unrelated pathogens up until at least three months after vaccination, which suggests that NK cells may contribute to the non-specific (heterologous) beneficial effects of BCG vaccination.
TL;DR: The state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer are reviewed and the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure‐based antigen design are described.
Abstract: In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2-3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure-based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines.
TL;DR: Vine effectiveness in the 2011-2012 season was modest overall, with lower effectiveness against the predominant A (H3N2) virus, which may be related to antigenic drift, but past history of vaccination might also play a role.
Abstract: (See the editorial commentary by Neuzil and Victor on pages 328–9.)
Influenza vaccines are unique in requiring regular changes in composition to match the antigenic drift of the circulating virus strains [1]. They currently are recommended annually in the United States for all persons aged ≥6 months [2] and are composed of 3 strains representing influenza A (H3N2), A (H1N1), and B viruses, some of which may be new in a particular year and some of which may not. Because 2 distinct lineages of type B circulate, strains from both will soon be incorporated into what will then be a quadrivalent vaccine [3]. There is ample evidence that influenza vaccine effectiveness (VE) varies not only by virus type (subtype) but also from year to year [4]. A number of explanations for these variations have been suggested, including antigenic match between vaccine and circulating strains, the age and health status of vaccine recipients, and the time between vaccine receipt and occurrence of the seasonal outbreak.
To monitor variation in VE, many countries have begun to conduct annual evaluations [5–9]. Various observational methods have been used, but most involve laboratory confirmation of illnesses as influenza and documentation of influenza vaccine receipt. Since the 2008–2009 influenza season, multiple centers in the United States have collaborated annually to estimate VE through the Influenza Vaccine Effectiveness (Flu VE) Network. This network examines the effectiveness of influenza vaccines in preventing medically attended acute respiratory illnesses caused by influenza. The network has quantified vaccine protection during seasonal outbreaks and has also demonstrated the effectiveness of the H1N1 pandemic vaccine once it became available in 2009 [5, 6].
We report here estimates of effectiveness of the 2011–2012 influenza vaccines, with special reference to protection against each circulating influenza virus and the effect of prior vaccination on estimates [10]. The influenza season was mild overall and peaked nationally in March 2012 with circulation of type A (H3N2) and A (H1N1) pdm09 viruses, plus type B viruses from both lineages [11].
TL;DR: The inactivated EV71 vaccine elicited EV 71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease, in healthy children 6 to 71 months of age in China.
Abstract: Background Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed. Methods We conducted a randomized, double-blind, placebo-controlled phase 3 trial involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous Region, China. Two doses of an inactivated EV71 vaccine or placebo were administered intramuscularly, with a 4-week interval between doses, and children were monitored for up to 11 months. The primary end point was protection against hand, foot, and mouth disease caused by EV71. Results A total of 12,000 children were randomly assigned to receive vaccine or placebo. Serum neutralizing antibodies were assessed in 549 children who received the vaccine. The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4% (95% confidence interval [CI], 92.9 to 99.0) according to the intention-to-trea...
TL;DR: It is shown that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques, and generated, for the first time, durable protection against lethal E BOV challenge.
Abstract: A chimpanzee adenovirus-based vaccination approach elicits acute and long-term protection against ebolavirus challenge in nonhuman primates.
TL;DR: Rates of invasive pneumococcal disease among children in South Africa fell substantially by 2012, and reductions in the rates of disease caused by PCV7 serotypes among both children and adults most likely reflect the direct and indirect effects of vaccination.
Abstract: BackgroundIn South Africa, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2009 with a three-dose schedule for infants at 6, 14, and 36 weeks of age; a 13-valent vaccine (PCV13) replaced PCV7 in 2011. In 2012, it was estimated that 81% of 12-month-old children had received three doses of vaccine. We assessed the effect of vaccination on invasive pneumococcal disease. MethodsWe conducted national, active, laboratory-based surveillance for invasive pneumococcal disease. We calculated the change in the incidence of the disease from a prevaccine (baseline) period (2005 through 2008) to postvaccine years 2011 and 2012, with a focus on high-risk age groups. ResultsSurveillance identified 35,192 cases of invasive pneumococcal disease. The rates among children younger than 2 years of age declined from 54.8 to 17.0 cases per 100,000 person-years from the baseline period to 2012, including a decline from 32.1 to 3.4 cases per 100,000 person-years in disease caused by PCV7 serotypes (−89%; 95% con...
TL;DR: A first-in-human trial of a prime-boost vaccine strategy for HCV, with durable, broad, sustained, and balanced T cell responses, characteristic of those associated with viral control, paving the way for the first efficacy studies of a prophylactic HCV vaccine.
Abstract: A protective vaccine against hepatitis C virus (HCV) remains an unmet clinical need. HCV infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular cancer. Animal challenge experiments, immunogenetics studies, and assessment of host immunity during acute infection highlight the critical role that effective T cell immunity plays in viral control. In this first-in-man study, we have induced antiviral immunity with functional characteristics analogous to those associated with viral control in natural infection, and improved upon a vaccine based on adenoviral vectors alone. We assessed a heterologous prime-boost vaccination strategy based on a replicative defective simian adenoviral vector (ChAd3) and modified vaccinia Ankara (MVA) vector encoding the NS3, NS4, NS5A, and NS5B proteins of HCV genotype 1b. Analysis used single-cell mass cytometry and human leukocyte antigen class I peptide tetramer technology in healthy human volunteers. We show that HCV-specific T cells induced by ChAd3 are optimally boosted with MVA, and generate very high levels of both CD8 + and CD4 + HCV-specific T cells targeting multiple HCV antigens. Sustained memory and effector T cell populations are generated, and T cell memory evolved over time with improvement of quality (proliferation and polyfunctionality) after heterologous MVA boost. We have developed an HCV vaccine strategy, with durable, broad, sustained, and balanced T cell responses, characteristic of those associated with viral control, paving the way for the first efficacy studies of a prophylactic HCV vaccine.
TL;DR: A novel method for generating MERS- coV and SARS-CoV full-length spike nanoparticles, which in combination with adjuvants are able to produce high titer antibodies in mice is described.
TL;DR: Significant changes in B. pertussis populations have been observed after the introduction of vaccinations, suggesting a role for pathogen adaptation in the persistence and resurgence of pertussi.
Abstract: Pertussis or whooping cough has persisted and resurged in the face of vaccination and has become one of the most prevalent vaccine-preventable diseases in Western countries. The high circulation rate of Bordetella pertussis poses a threat to infants that have not been (completely) vaccinated and for whom pertussis is a severe, life-threatening, disease. The increase in pertussis is mainly found in age groups in which immunity has waned and this has resulted in the perception that waning immunity is the main or exclusive cause for the resurgence of pertussis. However, significant changes in B. pertussis populations have been observed after the introduction of vaccinations, suggesting a role for pathogen adaptation in the persistence and resurgence of pertussis. These changes include antigenic divergence with vaccine strains and increased production of pertussis toxin. Antigenic divergence will affect both memory recall and the efficacy of antibodies, while higher levels of pertussis toxin may increase suppression of the innate and acquired immune system. We propose these adaptations of B. pertussis have decreased the period in which pertussis vaccines are effective and thus enhanced the waning of immunity. We plead for a more integrated approach to the pertussis problem which includes the characteristics of the vaccines, the B. pertussis populations and the interaction between the two.