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Frontiers in Immunology 2021There is a significant research gap in meta-analysis on the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines. This study analyzed the efficacy of... (Meta-Analysis)
Meta-Analysis
There is a significant research gap in meta-analysis on the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines. This study analyzed the efficacy of COVID-19 vaccines. Published phase I, phase II, and phase III trials analyzing safety and immunogenicity and phase III randomized clinical trials evaluating the efficacy of COVID-19 vaccines were included. We searched MEDLINE, Scopus, and The Lancet for published articles evaluating the relative reduction in COVID-19 risk after vaccination. Selected literatures were published between December 15, 2019 and May 15, 2021 on the safety, efficacy, and immunogenicity of COVID-19 vaccines. This meta-analysis included studies that confirmed cases of COVID-19 using reverse transcriptase polymerase chain reaction. This study detected 8,926 eligible research articles published on COVID-19 vaccines. Of these, 25 studies fulfilled the inclusion criteria. Among the selected articles, 19 randomized clinical trials, 2 non-randomized clinical trials, and 3 observational studies were analyzed. Seven (28%) studies were included in the meta-analysis. The efficacy of the adenovirus vector vaccine was 73% (95% CI = 69-77) and that of the messenger RNA (mRNA) vaccine was 85% (95% CI = 82-88) in participants aged ≥18 years. There are no reports of clinical trials in participants aged under 16 years. The production of neutralizing antibodies against receptor-binding domains (RBDs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in >90% of the vaccinated samples was reported within 0-30 days of the first or the second dose of the vaccine. Pain at the injection site was the most common local symptom in people receiving mRNA vaccines (29%-85% of participants). Fever (0.2%-95%) was the most prevalent in people receiving adenovirus vector vaccines, and fatigue (8.4%-55%) was the most common side effect in people receiving the mRNA vaccines. Studies suggest that mRNA vaccines and adenovirus vector vaccines can provide moderate to high protection against COVID-19 infection in people over 18 years. Evidence of the long-term protection of the vaccines in people aged under 16 years against the multiple variants of COVID-19 are limited. This study will provide an integrated evaluation on the efficacy, safety, and immunogenicity of the COVID-19 vaccines.
Topics: Adolescent; Adult; Aged; Antibodies, Neutralizing; COVID-19; COVID-19 Vaccines; Humans; Immunogenicity, Vaccine; Injections, Intramuscular; Middle Aged; Pain; Randomized Controlled Trials as Topic; SARS-CoV-2; Young Adult
PubMed: 34707602
DOI: 10.3389/fimmu.2021.714170 -
Italian Journal of Pediatrics Jul 2023Robust routine immunization schedules for pertussis-containing vaccines have been applied for years, but pertussis outbreaks remain a worldwide problem. This study aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Robust routine immunization schedules for pertussis-containing vaccines have been applied for years, but pertussis outbreaks remain a worldwide problem. This study aimed to investigate the association between vaccine hesitancy and pertussis in infants and children.
METHODS
We searched PubMed, Cochrane, Web of Science, Embase, and China National Knowledge Internet for studies published between January 2012 and June 2022. This study included case-control and cohort studies that assessed the association between childhood/maternal vaccine hesitancy and odds ratios (ORs), risk ratios (RRs), and vaccine effectiveness (VE) related to pertussis in infants and children [Formula: see text] 9 years old. ORs/VEs with a 95% confidence interval (CI) were calculated. Random-effects meta-analysis models were used for appropriate pooled estimates, and heterogeneity was assessed using [Formula: see text]. Cumulative meta-analysis and subgroup analyses stratified by study characteristics were performed.
RESULTS
Twenty-two studies were included, with a mean quality score of 7.0 (range 6.0-9.0). Infants and children with pertussis were associated with higher vaccine hesitancy to all doses (OR = 4.12 [95% CI: 3.09-5.50]). The highest OR was between children who were unvaccinated over four doses and children who were fully vaccinated (OR = 14.26 [95%CI: 7.62-26.70]); childhood vaccine delay was not statistically significantly associated with pertussis risk (OR = 1.18 [95% CI: 0.74-1.89]). Maternal vaccine hesitancy was associated with significantly higher pertussis risk in infants aged 2 and 3 months old, with higher pertussis ORs in infants [Formula: see text] 2 months old (OR = 6.02 [95%CI: 4.31-8.50], OR = 5.14 [95%CI: 1.95-13.52] for infants [Formula: see text] 2 and [Formula: see text] 3 months old, respectively). Maternal and childhood VEs were high in reducing pertussis infection in infants and children. The administration time of maternal vaccination had little effect on VE.
CONCLUSION
Vaccine hesitancy increased pertussis risks in infants and children. Ensuring that children receive up-to-date pertussis vaccines is essential; short delays in receiving childhood vaccinations may be unimportant. Maternal vaccinations for pertussis should be encouraged.
Topics: Child; Infant; Humans; Whooping Cough; Vaccination Hesitancy; Vaccination; Immunization Schedule; Vaccines
PubMed: 37443026
DOI: 10.1186/s13052-023-01495-8 -
Vaccine Sep 2022Human papillomavirus (HPV) vaccines were first licensed as a three-dose series. Two doses are now widely recommended in some age groups; there are data suggesting high... (Review)
Review
BACKGROUND
Human papillomavirus (HPV) vaccines were first licensed as a three-dose series. Two doses are now widely recommended in some age groups; there are data suggesting high efficacy with one dose. We updated a systematic literature review of HPV vaccine effectiveness by number of doses in observational studies.
METHODS
We searched Medline and Embase databases from January 1, 2007, through September 29, 2021. Data were extracted and summarized in a narrative synthesis. We also conducted quality assessments for bias due to selection, information, and confounding.
RESULTS
Overall, 35 studies were included; all except one were conducted within the context of a recommended three-dose schedule. Evaluations were in countries that used bivalent HPV vaccine (seven), quadrivalent HPV vaccine (27) or both (one). Nine evaluated effectiveness against HPV infection, ten anogenital warts, and 16 cervical abnormalities. All studies were judged to have moderate or serious risk of bias. The biases rated as serious would likely result in lower effectiveness with fewer doses. Investigators attempted to control for or stratify by potentially important variables, such as age at vaccination. Eight studies evaluated impact of buffer periods (lag time) for case counting and 10 evaluated different intervals between doses for two-dose vaccine recipients. Studies that stratified by vaccination age found higher effectiveness with younger age at vaccination, although differences were not all formally tested. Most studies found highest estimates of effectiveness with three doses; significant effectiveness was found among 28/29 studies that evaluated three doses, 19/29 that evaluated two doses, and 18/30 that evaluated one dose. Some studies that adjusted or stratified analyses by age at vaccination found similar effectiveness with three, two and one doses.
CONCLUSION
Observational studies of HPV vaccine effectiveness have many biases. Studies examining persons vaccinated prior to sexual activity and using methods to reduce sources of bias are needed for valid effectiveness estimates.
Topics: Alphapapillomavirus; Female; Humans; Immunization Programs; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Vaccination; Vaccine Efficacy
PubMed: 35965239
DOI: 10.1016/j.vaccine.2022.06.065 -
International Journal of Infectious... Sep 2018For Ebola vaccine development, antibody response is a major endpoint although its determinants are not well known. We aimed to review Ebola vaccine studies and to assess... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
For Ebola vaccine development, antibody response is a major endpoint although its determinants are not well known. We aimed to review Ebola vaccine studies and to assess factors associated with antibody response variability in humans.
METHODS
We searched PubMed and Scopus for preventive Ebola vaccine studies in humans or non-human primates (NHP), published up to February 2018. For each vaccination group with Ebola Zaire antibody titre measurements after vaccination, data about antibody response and its potential determinants were extracted. A random-effects meta-regression was conducted including human groups with at least 8 individuals.
RESULTS
We reviewed 49 studies (202 vaccination groups including 74 human groups) with various vaccine platforms and antigen inserts. Mean antibody titre was slightly higher in NHP (3.10, 95% confidence interval [293; 327]) than in humans (2.75 [257; 293]). Vaccine platform (p<0·001) and viral strain used for antibody detection (p<0·001) were associated with antibody response in humans, but adjusted heterogeneity remained at 95%.
CONCLUSIONS
Various platforms have been evaluated in humans, including Ad26, Ad5, ChimpAd3, DNA, MVA, and VSV. In addition to platforms, viral strain used for antibody detection influences antibody response. However, variability remained mostly unexplained. Therefore, comparison of vaccine immunogenicity needs randomised controlled trials.
Topics: Animals; Antibodies, Viral; Clinical Studies as Topic; Ebola Vaccines; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Vaccination
PubMed: 29981944
DOI: 10.1016/j.ijid.2018.06.022 -
The Lancet. Infectious Diseases Feb 2019Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes...
BACKGROUND
Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990-2015.
METHODS
We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. We grouped countries into 14 regions and analysed data for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164.
FINDINGS
This systematic review and global survey yielded 2203 datasets with 383 519 samples from 116 countries in 1990-2015. Globally, subtype C accounted for 46·6% (16 280 897/34 921 639 of PLHIV) of all HIV-1 infections in 2010-15. Subtype B was responsible for 12·1% (4 235 299/34 921 639) of infections, followed by subtype A (10·3%; 3 587 003/34 921 639), CRF02_AG (7·7%; 2 705 110/34 921 639), CRF01_AE (5·3%; 1 840 982/34 921 639), subtype G (4·6%; 1 591 276/34 921 639), and subtype D (2·7%; 926 255/34 921 639). Subtypes F, H, J, and K combined accounted for 0·9% (311 332/34 921 639) of infections. Other CRFs accounted for 3·7% (1 309 082/34 921 639), bringing the proportion of all CRFs to 16·7% (5 844 113/34 921 639). URFs constituted 6·1% (2 134 405/34 921 639), resulting in recombinants accounting for 22·8% (7 978 517/34 921 639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005-15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time.
INTERPRETATION
Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines.
FUNDING
None.
Topics: AIDS Vaccines; Genetic Variation; Genome, Viral; Genotype; Genotyping Techniques; Global Health; HIV Infections; HIV-1; Humans; Serogroup; Serotyping; Surveys and Questionnaires
PubMed: 30509777
DOI: 10.1016/S1473-3099(18)30647-9 -
Innovation (Cambridge (Mass.)) May 2021COVID-19 has spread globally to over 200 countries with more than 40 million confirmed cases and one million deaths as of November 1, 2020. The SARS-CoV-2 virus, leading... (Review)
Review
COVID-19 has spread globally to over 200 countries with more than 40 million confirmed cases and one million deaths as of November 1, 2020. The SARS-CoV-2 virus, leading to COVID-19, shows extremely high rates of infectivity and replication, and can result in pneumonia, acute respiratory distress, or even mortality. SARS-CoV-2 has been found to continue to rapidly evolve, with several genomic variants emerging in different regions throughout the world. In addition, despite intensive study of the spike protein, its origin, and molecular mechanisms in mediating host invasion are still only partially resolved. Finally, the repertoire of drugs for COVID-19 treatment is still limited, with several candidates still under clinical trial and no effective therapeutic yet reported. Although vaccines based on either DNA/mRNA or protein have been deployed, their efficacy against emerging variants requires ongoing study, with multivalent vaccines supplanting the first-generation vaccines due to their low efficacy against new strains. Here, we provide a systematic review of studies on the epidemiology, immunological pathogenesis, molecular mechanisms, and structural biology, as well as approaches for drug or vaccine development for SARS-CoV-2.
PubMed: 33997827
DOI: 10.1016/j.xinn.2021.100116 -
Journal of Medical Virology Apr 2021The year 2020 started with the emergence of novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19 infection. Soon after...
The year 2020 started with the emergence of novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19 infection. Soon after the first evidence was reported in Wuhan, China, the World Health Organization declared global public health emergency and imminent need to understand the pathogenicity of the virus was required in limited time. Once the genome sequence of the virus was delineated, scientists across the world started working on the development of vaccines. Although, some laboratories have been using previously developed vaccine platforms from severe acute respiratory syndrome coronavirus (SARS) and middle east respiratory syndrome-related coronavirus and apply them in COVID-19 vaccines due to genetic similarities between coronaviruses. We have conducted a literature review to assess the background and current status of COVID-19 vaccines. The worldwide implementation and strategies for COVID-19 vaccine development are summarized from studies reported in years 2015-2020. While discussing the vaccine candidates, we have also explained interpretative immune responses of SARS-CoV-2 infection. There are several vaccine candidates at preclinical and clinical stages; however, only 42 vaccines are under clinical trials. Therefore, more industry collaborations and financial supports to COVID-19 studies are needed for mass-scale vaccine development. To develop effective vaccine platforms against SARS-CoV-2, the genetic resemblance with other coronaviruses are being evaluated which may further promote fast-track trials on previously developed SARS-CoV vaccines.
Topics: COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2; Vaccines, DNA; Vaccines, Inactivated; Vaccines, Live, Unattenuated; Vaccines, Subunit
PubMed: 33270225
DOI: 10.1002/jmv.26709 -
The Lancet. Microbe Feb 2024The high strain diversity of Streptococcus pyogenes serves as a major obstacle to vaccine development against this leading global pathogen. We did a systematic review of... (Review)
Review
The high strain diversity of Streptococcus pyogenes serves as a major obstacle to vaccine development against this leading global pathogen. We did a systematic review of studies in PubMed, MEDLINE, and Embase that reported the global distribution of S pyogenes emm-types and emm-clusters from Jan 1, 1990, to Feb 23, 2023. 212 datasets were included from 55 countries, encompassing 74 468 bacterial isolates belonging to 211 emm-types. Globally, an inverse correlation was observed between strain diversity and the UNDP Human Development Index (HDI; r=-0·72; p<0·0001), which remained consistent upon subanalysis by global region and site of infection. Greater strain diversity was associated with a lower HDI, suggesting the role of social determinants in diseases caused by S pyogenes. We used a population-weighted analysis to adjust for the disproportionate number of epidemiological studies from high-income countries and identified 15 key representative isolates as vaccine targets. Strong strain type associations were observed between the site of infection (invasive, skin, and throat) and several streptococcal lineages. In conclusion, the development of a truly global vaccine to reduce the immense burden of diseases caused by S pyogenes should consider the multidimensional diversity of the pathogen, including its social and environmental context, and not merely its geographical distribution.
Topics: Humans; Streptococcus pyogenes; Streptococcal Infections; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Vaccines
PubMed: 38070538
DOI: 10.1016/S2666-5247(23)00318-X -
Biomedicine & Pharmacotherapy =... Dec 2021Dengue virus (DENV) is a global health threat causing about half of the worldwide population to be at risk of infection, especially the people living in tropical and...
Dengue virus (DENV) is a global health threat causing about half of the worldwide population to be at risk of infection, especially the people living in tropical and subtropical area. Although the dengue disease caused by dengue virus (DENV) is asymptomatic and self-limiting in most people with first infection, increased severe dengue symptoms may be observed in people with heterotypic secondary DENV infection. Since there is a lack of specific antiviral medication, the development of dengue vaccines is critical in the prevention and control this disease. Several targets and strategies in the development of dengue vaccine have been demonstrated. Currently, Dengvaxia, a live-attenuated chimeric yellow-fever/tetravalent dengue vaccine (CYD-TDV) developed by Sanofi Pasteur, has been licensed and approved for clinical use in some countries. However, this vaccine has demonstrated low efficacy in children and dengue-naïve individuals and also increases the risk of severe dengue in young vaccinated recipients. Accordingly, many novel strategies for the dengue vaccine are under investigation and development. Here, we conducted a systemic literature review according to PRISMA guidelines to give a concise overview of various aspects of the vaccine development process against DENVs, mainly targeting five potential strategies including live attenuated vaccine, inactivated virus vaccine, recombinant subunit vaccine, viral-vector vaccine, and DNA vaccine. This study offers the comprehensive view of updated information and current progression of immunogen selection as well as strategies of vaccine development against DENVs.
Topics: Animals; Dengue; Dengue Vaccines; Dengue Virus; Humans; Treatment Outcome; Vaccine Development; Vaccine Efficacy; Vaccines, Attenuated; Vaccines, DNA; Vaccines, Inactivated; Vaccines, Synthetic; Viral Envelope Proteins; Viral Nonstructural Proteins
PubMed: 34634560
DOI: 10.1016/j.biopha.2021.112304 -
Frontiers in Immunology 2022Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of...
BACKGROUND
Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of research efforts to combat this major global health burden, there is no approved prophylactic vaccine against EBV. To facilitate the rational design and assessment of an effective vaccine, we systematically reviewed pre-clinical and clinical prophylactic EBV vaccine studies to determine the antigens, delivery platforms, and animal models used in these studies.
METHODS
We searched Cochrane Library, ClinicalTrials.gov, Embase, PubMed, Scopus, Web of Science, WHO's Global Index Medicus, and Google Scholar from inception to June 20, 2020, for EBV prophylactic vaccine studies focused on humoral immunity.
RESULTS
The search yielded 5,614 unique studies. 36 pre-clinical and 4 clinical studies were included in the analysis after screening against the exclusion criteria. In pre-clinical studies, gp350 was the most commonly used immunogen (33 studies), vaccines were most commonly delivered as monomeric proteins (12 studies), and mice were the most used animal model to test immunogenicity (15 studies). According to an adaptation of the CAMARADES checklist, 4 pre-clinical studies were rated as very high, 5 as high, 13 as moderate quality, 11 as poor, and 3 as very poor. In clinical studies, gp350 was the sole vaccine antigen, delivered in a vaccinia platform (1 study) or as a monomeric protein (3 studies). The present study was registered in PROSPERO (CRD42020198440).
CONCLUSIONS
Four major obstacles have prevented the development of an effective prophylactic EBV vaccine: undefined correlates of immune protection, lack of knowledge regarding the ideal EBV antigen(s) for vaccination, lack of an appropriate animal model to test vaccine efficacy, and lack of knowledge regarding the ideal vaccine delivery platform. Our analysis supports a multivalent antigenic approach including two or more of the five main glycoproteins involved in viral entry (gp350, gB, gH/gL, gp42) and a multimeric approach to present these antigens. We anticipate that the application of two underused challenge models, rhesus macaques susceptible to rhesus lymphocryptovirus (an EBV homolog) and common marmosets, will permit the establishment of correlates of immune protection and attainment of more generalizable data.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440, identifier PROSPERO I.D. CRD4202019844.
Topics: Animals; Disease Models, Animal; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Infectious Mononucleosis; Macaca mulatta; Mice; Serologic Tests
PubMed: 35493498
DOI: 10.3389/fimmu.2022.867918