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Pathogens (Basel, Switzerland) Dec 2023Developing a safe and effective vaccine against the hepatitis C virus (HCV) remains a top priority for global health. Despite recent advances in antiviral therapies, the... (Review)
Review
Developing a safe and effective vaccine against the hepatitis C virus (HCV) remains a top priority for global health. Despite recent advances in antiviral therapies, the high cost and limited accessibility of these treatments impede their widespread application, particularly in resource-limited settings. Therefore, the development of the HCV vaccine remains a necessity. This review article analyzes the current technologies, future prospects, strategies, HCV genomic targets, and the governmental role in HCV vaccine development. We discuss the current epidemiological landscape of HCV infection and the potential of HCV structural and non-structural protein antigens as vaccine targets. In addition, the involvement of government agencies and policymakers in supporting and facilitating the development of HCV vaccines is emphasized. We explore how vaccine development regulatory channels and frameworks affect research goals, funding, and public health policy. The significance of international and public-private partnerships in accelerating the development of an HCV vaccine is examined. Finally, the future directions for developing an HCV vaccine are discussed. In conclusion, the review highlights the urgent need for a preventive vaccine to fight the global HCV disease and the significance of collaborative efforts between scientists, politicians, and public health organizations to reach this important public health goal.
PubMed: 38251345
DOI: 10.3390/pathogens13010038 -
Human Vaccines & Immunotherapeutics Dec 2023Immunocompetent adults with certain medical and behavioral factors are at increased risk of pneumococcal disease. In some countries, sequential vaccination with...
Phase 3 trial to evaluate the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, followed by 23-valent pneumococcal polysaccharide vaccine 6 months later, in at-risk adults 18-49 years of age (PNEU-DAY): A subgroup analysis by baseline risk factors.
Immunocompetent adults with certain medical and behavioral factors are at increased risk of pneumococcal disease. In some countries, sequential vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for at-risk adults. This subgroup analysis from a phase 3 study evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 6 months later by PPSV23, in immunocompetent adults 18-49 years of age with pre-defined risk factors for pneumococcal disease. Safety and immunogenicity post-vaccination were analyzed by type and baseline number of risk factors for pneumococcal disease (1 and ≥2 risk factors). This analysis included 1,131 participants randomized 3:1 to receive either V114 or PCV13, followed by PPSV23. The majority (73.1%) of participants had at least one risk factor. Safety and tolerability profiles of V114 and PCV13 were similar across risk factor groups. V114 administered either alone or sequentially with PPSV23 6 months later was immunogenic for all 15 serotypes, including those not contained in PCV13, regardless of the number of baseline risk factors. V114 has the potential to broaden serotype coverage for at-risk adults.
Topics: Humans; Adult; Streptococcus pneumoniae; Vaccines, Conjugate; Double-Blind Method; Pneumococcal Infections; Pneumococcal Vaccines; Antibodies, Bacterial; Immunogenicity, Vaccine
PubMed: 36864601
DOI: 10.1080/21645515.2023.2177066 -
Human Vaccines & Immunotherapeutics Aug 2023This open-labeled non-inferiority trial evaluated immunogenicity and reactogenicity of heterologous and homologous COVID-19 vaccination schedules in pregnant Thai women.... (Randomized Controlled Trial)
Randomized Controlled Trial
This open-labeled non-inferiority trial evaluated immunogenicity and reactogenicity of heterologous and homologous COVID-19 vaccination schedules in pregnant Thai women. 18-45-year-old pregnant women with no history of COVID-19 infection or vaccination and a gestational age of ≥12 weeks were randomized 1:1:1 into three two-dose primary series scheduled 4 weeks apart: BNT162b2-BNT162b2 (Group 1), ChAdOx1-BNT162b2 (Group 2), and CoronaVac-BNT162b2 (Group 3). Serum antibody responses, maternal and cord blood antibody levels at delivery, and adverse events (AEs) following vaccination until delivery were assessed. The 124 enrolled participants had a median age of 31 (interquartile range [IQR] 26.0-35.5) years and gestational age of 23.5 (IQR 18.0-30.0) weeks. No significant difference in anti-receptor binding domain (RBD) IgG were observed across arms at 2 weeks after the second dose. Neutralizing antibody geometric mean titers against the ancestral Wuhan strain were highest in Group 3 (258.22, 95% CI [187.53, 355.56]), followed by Groups 1 (187.47, 95% CI [135.15, 260.03]) and 2 (166.63, 95% CI [124.60, 222.84]). Cord blood anti-RBD IgG was correlated with, and equal to or higher than, maternal levels at delivery ( = 0.719, < .001) and inversely correlated with elapsed time after the second vaccination ( = -0.366, < .001). No significant difference in cord blood antibody levels between groups were observed. Local and systemic AEs were mild-to-moderate and more frequent in Group 2. Heterologous schedules of CoronaVac-BNT162b2 or ChAdOx1-BNT162b2 induced immunogenicity on-par with BNT162b2-BNT162b2 and may be considered as alternative schedules for primary series in pregnant women in mRNA-limited vaccine settings.
Topics: Adolescent; Adult; Female; Humans; Infant; Middle Aged; Pregnancy; Young Adult; Antibodies, Viral; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Immunogenicity, Vaccine; Immunoglobulin G; Pregnancy Complications, Infectious; Pregnant Women; Vaccination
PubMed: 37439770
DOI: 10.1080/21645515.2023.2228670 -
International Journal of Biological... Feb 2024Self-assembly involves a set of molecules spontaneously interacting in a highly coordinated and dynamic manner to form a specific supramolecular structure having new and... (Review)
Review
Self-assembly involves a set of molecules spontaneously interacting in a highly coordinated and dynamic manner to form a specific supramolecular structure having new and clearly defined properties. Many examples of this occur in nature and many more came from research laboratories, with their number increasing every day via ongoing research concerning complex biomolecules and the possibility of harnessing it when developing new applications. As a phenomenon, self-assembly has been described on very different types of molecules (biomolecules including), so this review focuses on what is known about peptide self-assembly, its origins, the forces behind it, how the properties of the resulting material can be tuned in relation to experimental considerations, some biotechnological applications (in which the main protagonists are peptide sequences capable of self-assembly) and what is yet to be tuned regarding their research and development.
Topics: Peptides; Biotechnology; Vaccine Development
PubMed: 38145690
DOI: 10.1016/j.ijbiomac.2023.128944 -
JAMA Network Open Apr 2024Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay.
IMPORTANCE
Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay.
OBJECTIVE
To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment.
DESIGN, SETTING, AND PARTICIPANTS
This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022. Eligible participants included adults with MS who completed immunization for hepatitis B virus (HBV), hepatitis A virus (HAV), and COVID-19 during natalizumab therapy. Data analysis was conducted from November 2022 to February 2023.
EXPOSURES
Patients were categorized according to their time receiving natalizumab treatment at the time of vaccine administration as short-term (≤1 year) or long-term (>1 year).
MAIN OUTCOMES AND MEASURES
Demographic, clinical, and radiological characteristics were collected during the year before vaccination (prevaccination period) and the year after vaccination (postvaccination period). Seroprotection rates and postvaccination immunoglobulin G titers were determined for each vaccine within both periods. Additionally, differences in annualized relapse rate (ARR), new T2 lesions (NT2L), Expanded Disability Status Scale (EDSS) scores, and John Cunningham virus (JCV) serostatus between the 2 periods were assessed.
RESULTS
Sixty patients with MS (mean [SD] age, 43.2 [9.4] years; 44 female [73.3%]; 16 male [26.7%]; mean [SD] disease duration, 17.0 [8.7] years) completed HBV, HAV, and mRNA COVID-19 immunization during natalizumab treatment, with 12 patients in the short-term group and 48 patients in the long-term group. The global seroprotection rate was 93% (95% CI, 86%-98%), with individual vaccine rates of 92% for HAV (95% CI, 73%-99%), 93% for HBV (95% CI, 76%-99%), and 100% for the COVID-19 messenger RNA vaccine (95% CI, 84%-100%). Between the prevaccination and postvaccination periods there was a significant reduction in the mean (SD) ARR (0.28 [0.66] vs 0.01 [0.12]; P = .004) and median (IQR) NT2L (5.00 [2.00-10.00] vs 0.81 [0.00-0.50]; P = .01). No changes in disability accumulation were detected (median [IQR] EDSS score 3.5 [2.0-6.0] vs 3.5 [2.0-6.0]; P = .62). No differences in safety and immunogenicity were observed for all vaccines concerning the duration of natalizumab treatment.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that immunization with inactivated vaccines during natalizumab therapy was both safe and immunogenic, regardless of the treatment duration. Natalizumab may be a valuable option for proper immunization, averting treatment delays in patients with highly active MS; however, this strategy needs to be formally evaluated.
Topics: Adult; Female; Humans; Male; Cohort Studies; Multiple Sclerosis; Natalizumab; Prospective Studies; Vaccines, Inactivated; Immunogenicity, Vaccine; Middle Aged
PubMed: 38607624
DOI: 10.1001/jamanetworkopen.2024.6345 -
Vaccine Aug 2023Coronavirus disease (COVID-19) is still spreading rapidly worldwide, and a safe, effective, and cheap vaccine is still required to combat the COVID-19 pandemic. Here, we...
Coronavirus disease (COVID-19) is still spreading rapidly worldwide, and a safe, effective, and cheap vaccine is still required to combat the COVID-19 pandemic. Here, we report a recombinant bivalent COVID-19 vaccine containing the RBD proteins of the prototype strain and beta variant. Immunization studies in mice demonstrated that this bivalent vaccine had far greater immunogenicity than the ZF2001, a marketed monovalent recombinant protein COVID-19 vaccine, and exhibited good immunization effects against the original COVID-19 strain and various variants. Rhesus macaque challenge experiments showed that this bivalent vaccine drastically decreased the lung viral load and reduced lung lesions in SARS-CoV-2 (the causative virus of COVID-19)-infected rhesus macaques. In summary, this bivalent vaccine showed immunogenicity and protective efficacy that was far superior to the monovalent recombinant protein vaccine against the prototype strain and provided an important basis for developing broad-spectrum COVID-19 vaccines.
Topics: Animals; Mice; Humans; Macaca mulatta; COVID-19 Vaccines; Vaccines, Combined; Pandemics; COVID-19; SARS-CoV-2; Antibodies, Viral; Antibodies, Neutralizing; Immunogenicity, Vaccine; Spike Glycoprotein, Coronavirus
PubMed: 37451875
DOI: 10.1016/j.vaccine.2023.06.086 -
Microbiology Spectrum Dec 2023The development of safe and effective vaccines is needed to control the transmission of coronavirus disease 2019 (COVID-19). Synthetic DNA vaccines represent a promising...
The development of safe and effective vaccines is needed to control the transmission of coronavirus disease 2019 (COVID-19). Synthetic DNA vaccines represent a promising platform in response to such outbreaks. Here, DNA vaccine candidates were developed using an optimized antibiotic-resistance gene-free asd-pVAX1 vector. An optimized flagellin (FliC) adjuvant was designed by fusion expression to increase the immunogenicity of the S1 antigen. S1 and S1-FliCΔD2D3 proteins were strongly expressed in mammalian cells. The FliCΔD2D3-adjuvanted DNA vaccine induced Th1/Th2-mixed immune responses and high titers of neutralizing antibodies. This study provides crucial information regarding the selection of a safer DNA vector and adjuvant for vaccine development. Our FliCΔD2D3-adjuvanted S1 DNA vaccine is more potent at inducing both humoral and cellular immune responses than S1 alone. This finding provides a new idea for the development of novel DNA vaccines against COVID-19 and could be further applied for the development of other vaccines.
Topics: Humans; Animals; Mice; Salmonella typhimurium; Vaccines, DNA; SARS-CoV-2; Flagellin; COVID-19 Vaccines; COVID-19; Adjuvants, Immunologic; Antibodies, Neutralizing; Antibodies, Viral; Immunogenicity, Vaccine; Mammals
PubMed: 37909745
DOI: 10.1128/spectrum.02549-23 -
Frontiers in Public Health 2023Infections with human papillomaviruses (HPV) are sexually transmitted and can cause cancer. In Germany, vaccination against HPV is recommended for girls and boys aged...
BACKGROUND
Infections with human papillomaviruses (HPV) are sexually transmitted and can cause cancer. In Germany, vaccination against HPV is recommended for girls and boys aged 9-17 years. We aimed to investigate HPV DNA prevalence, genotype distribution and vaccine effectiveness (VE) in women aged 20-25 years 10 years after the introduction of HPV vaccination in Germany (2018-2019), and compared these data to an equally designed study from 2010-2012.
METHODS
Seventy six geographical clusters were randomly selected, followed by random selection of 61 women aged 20-25 years per cluster. Participants performed cervicovaginal self-sampling and answered questions on demographics, sexual behaviour and HPV vaccination. Samples were tested for 18 high risk and nine low risk HPV genotypes. We performed chi-square tests, Fisher's exact test, unpaired Student's -test and proportion -test, and calculated crude and adjusted prevalence ratios (PR) and 95% CIs.
RESULTS
Of 7,858 contacted women a total of 1,226 agreed to participate. Of these, 94 women were positive for HPV types 16 and/or 18. HPV16 prevalence was 7.0% (95% CI 5.6-8.6) and HPV18 prevalence was 0.8% (95% CI 0.4-1.5). HPV6 and HPV11 were rare with only five (0.4%; 0.1-0.9) and one (0%; 95% CI 0.0-0.5) positive tests. Seven hundred fifty-seven women (62%) had received at least one HPV vaccine dose and 348 (28%) were vaccinated as currently recommended. Confounder-adjusted VE was 46.4% (95% CI 4.2-70.1) against HPV16/18 infection and 49.1% (95% CI 8.2-71.8) against infection with at least one HPV genotype covered by the quadrivalent HPV vaccine. Compared with the 2010-2012 study results, HPV16/18 prevalence dropped from 22.5% (95% CI 19.0-26.3) to 10.3% (95% CI 7.5-13.9; < 0.0001) in unvaccinated participants.
CONCLUSION
Vaccine-covered HPV genotypes were rare among 20-25 years old women in Germany and decreased compared to the time point shortly after the start of the HPV vaccination program. HPV prevalence of almost all vaccine-covered genotypes was strongly reduced in vaccinated participants. A decrease of HPV16 and HPV18 was even observed in unvaccinated participants, compared to 2010-2012 data, suggesting indirect protection of unvaccinated women. Low VE against HPV16/18 and HPV6/11/16/18 in our study might be attributable to study design in combination with the endpoint selection of (mainly transient) HPV DNA positivity.
Topics: Adult; Female; Humans; Young Adult; Germany; Human papillomavirus 16; Human papillomavirus 18; Human Papillomavirus Viruses; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Prevalence; Vaccine Efficacy
PubMed: 37719724
DOI: 10.3389/fpubh.2023.1204101 -
Human Vaccines & Immunotherapeutics Dec 2023This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or... (Randomized Controlled Trial)
Randomized Controlled Trial
This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC ( = 44), V114-IM ( = 45), or 13-valent PCV (PCV13)-SC ( = 44) at 3, 4, 5, and 12-15 months of age. Diphtheria, tetanus, and pertussis-inactivated poliovirus (DTaP-IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP-IPV at 1-month post-dose 3 (PD3). On days 1-14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP-IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.
Topics: Humans; Infant; Antibodies, Bacterial; East Asian People; Immunogenicity, Vaccine; Immunoglobulin G; Pneumococcal Infections; Pneumococcal Vaccines; Poliovirus Vaccine, Inactivated; Tetanus Toxoid; Vaccines, Conjugate; Vaccines, Combined
PubMed: 36882898
DOI: 10.1080/21645515.2023.2180973 -
BioRxiv : the Preprint Server For... Oct 2023Despite the success of global vaccination programs in slowing the spread of COVID-19, these efforts have been hindered by the emergence of new SARS-CoV-2 strains capable...
Despite the success of global vaccination programs in slowing the spread of COVID-19, these efforts have been hindered by the emergence of new SARS-CoV-2 strains capable of evading prior immunity. The mutation and evolution of SARS-CoV-2 have created a demand for persistent efforts in vaccine development. SARS-CoV-2 Spike protein has been the primary target for COVID-19 vaccine development, but it is also the hotspot of mutations directly involved in host susceptibility and immune evasion. Our ability to predict emerging mutants and select conserved epitopes is critical for the development of a broadly neutralizing therapy or a universal vaccine. In this article, we review the general paradigm of immune responses to COVID-19 vaccines, highlighting the immunological epitopes of Spike protein that are likely associated with eliciting protective immunity resulting from vaccination. Specifically, we analyze the structural and evolutionary characteristics of the SARS-CoV-2 Spike protein related to immune activation and function via the toll-like receptors (TLRs), B cells, and T cells. We aim to provide a comprehensive analysis of immune epitopes of Spike protein, thereby contributing to the development of new strategies for broad neutralization or universal vaccination.
PubMed: 37961687
DOI: 10.1101/2023.10.26.564184