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Clinical Infectious Diseases : An... Jun 2024The adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD) in ≥60-years-olds... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD) in ≥60-years-olds over 1 RSV season. We evaluated efficacy and safety of 1 RSVPreF3 OA dose and of 2 RSVPreF3 OA doses given 1 year apart against RSV-LRTD over 2 RSV seasons post-dose 1.
METHODS
In this phase 3, blinded trial, ≥60-year-olds were randomized (1:1) to receive RSVPreF3 OA or placebo pre-season 1. RSVPreF3 OA recipients were re-randomized (1:1) to receive a second RSVPreF3 OA dose (RSV_revaccination group) or placebo (RSV_1dose group) pre-season 2; participants who received placebo pre-season 1 received placebo pre-season 2 (placebo group). Efficacy of both vaccine regimens against RSV-LRTD was evaluated over 2 seasons combined (confirmatory secondary objective, success criterion: lower limits of 2-sided CIs around efficacy estimates >20%).
RESULTS
The efficacy analysis comprised 24 967 participants (RSV_1dose: 6227; RSV_revaccination: 6242; placebo: 12 498). Median efficacy follow-up was 17.8 months. Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.6-92.0%) against severe RSV-LRTD. Efficacy over 2 seasons of a first dose followed by revaccination was 67.1% (97.5% CI: 48.1-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.5-92.0%) against severe RSV-LRTD. Reactogenicity/safety of the revaccination dose were similar to dose 1.
CONCLUSIONS
One RSVPreF3 OA dose was efficacious against RSV-LRTD over 2 RSV seasons in ≥60-year-olds. Revaccination 1 year post-dose 1 was well tolerated but did not seem to provide additional efficacy benefit in the overall study population.
CLINICAL TRIALS REGISTRATION
ClinicalTrials.gov: NCT04886596.
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Male; Female; Respiratory Syncytial Virus, Human; Aged; Middle Aged; Viral Fusion Proteins; Antibodies, Viral; Aged, 80 and over; Seasons; Vaccine Efficacy; Double-Blind Method; Immunization, Secondary
PubMed: 38253338
DOI: 10.1093/cid/ciae010 -
Nature Communications May 2024The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was... (Meta-Analysis)
Meta-Analysis
The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validated correlate of protection after vaccination has been identified. Here we performed a systematic search and meta-analysis of the available data to test whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. We observe a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, consistent with the existing assumption that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, we predict the durability of protection after vaccination and the impact of dose spacing. We find that delaying the second dose of MVA-BN vaccination will provide more durable protection and may be optimal in an outbreak with limited vaccine stock. Although further work is required to validate this correlate, this study provides a quantitative evidence-based approach for using antibody measurements to predict the effectiveness of mpox vaccination.
Topics: Animals; Humans; Antibodies, Viral; Enzyme-Linked Immunosorbent Assay; Smallpox Vaccine; Vaccination; Vaccine Efficacy; Vaccinia; Monkeypox virus
PubMed: 38719852
DOI: 10.1038/s41467-024-48180-w -
Human Vaccines & Immunotherapeutics Dec 2023As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18... (Randomized Controlled Trial)
Randomized Controlled Trial
As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly ( < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.
Topics: Adolescent; Adult; Child; Female; Humans; Middle Aged; Young Adult; Antibodies, Neutralizing; Antibodies, Viral; Double-Blind Method; East Asian People; Human papillomavirus 16; Human papillomavirus 18; Immunogenicity, Vaccine; Papillomavirus Infections; Papillomavirus Vaccines; Vaccines, Combined
PubMed: 37249310
DOI: 10.1080/21645515.2023.2209001 -
Clinical Infectious Diseases : An... Oct 2023Individuals who receive allogeneic hematopoietic cell transplant (allo-HCT) are immunocompromised and at high risk of pneumococcal infections, especially in the months... (Randomized Controlled Trial)
Randomized Controlled Trial
A Phase 3, Randomized, Double-Blind, Comparator-Controlled Study to Evaluate Safety, Tolerability, and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, in Allogeneic Hematopoietic Cell Transplant Recipients (PNEU-STEM).
BACKGROUND
Individuals who receive allogeneic hematopoietic cell transplant (allo-HCT) are immunocompromised and at high risk of pneumococcal infections, especially in the months following transplant. This study evaluated the safety and immunogenicity of V114 (VAXNEUVANCE; Merck, Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA), a 15-valent pneumococcal conjugate vaccine (PCV), when given to allo-HCT recipients.
METHODS
Participants received 3 doses of V114 or PCV13 (Prevnar 13; Wyeth LLC) in 1-month intervals starting 3-6 months after allo-HCT. Twelve months after HCT, participants received either PNEUMOVAX 23 or a fourth dose of PCV (if they experienced chronic graft vs host disease). Safety was evaluated as the proportion of participants with adverse events (AEs). Immunogenicity was evaluated by measuring serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) for all V114 serotypes in each vaccination group.
RESULTS
A total of 274 participants were enrolled and vaccinated in the study. The proportions of participants with AEs and serious AEs were generally comparable between intervention groups, and the majority of AEs in both groups were of short duration and mild-to-moderate intensity. For both IgG GMCs and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at day 90.
CONCLUSIONS
V114 was well tolerated in allo-HCT recipients, with a generally comparable safety profile to PCV13. V114 induced comparable immune responses to PCV13 for the 13 shared serotypes, and was higher for V114 serotypes 22F and 33F. Study results support the use of V114 in allo-HCT recipients. Clinical Trials Registration. clinicaltrials.gov (NCT03565900) and European Union at EudraCT 2018-000066-11.
Topics: Humans; Vaccines, Conjugate; Transplant Recipients; Hematopoietic Stem Cell Transplantation; Antibodies, Bacterial; Pneumococcal Infections; Pneumococcal Vaccines; Double-Blind Method; Immunoglobulin G; Immunogenicity, Vaccine
PubMed: 37338158
DOI: 10.1093/cid/ciad349 -
Human Vaccines & Immunotherapeutics Aug 2023Dengue is caused by a mosquito-transmitted flavivirus. The disease is now endemic to many tropical and subtropical regions, manifesting as approximately 96 million...
An open-label, Phase 3 trial of TAK-003, a live attenuated dengue tetravalent vaccine, in healthy US adults: immunogenicity and safety when administered during the second half of a 24-month shelf-life.
Dengue is caused by a mosquito-transmitted flavivirus. The disease is now endemic to many tropical and subtropical regions, manifesting as approximately 96 million symptomatic cases of dengue each year. Clinical trials have shown TAK-003 (Qdenga®), a live attenuated dengue tetravalent vaccine, to be well-tolerated, immunogenic, and efficacious in adults with no prior exposure to dengue virus infection living in non-endemic regions, as well as in adults and children living in dengue-endemic areas. This open-label, single-arm phase 3 trial (NCT03771963) was conducted in two dengue non-endemic areas of the USA, and it evaluated the immunogenicity and safety of naturally-aged TAK-003 administered to adult participants. Overall, the immunogenicity data from this trial are consistent with those reported from other TAK-003 phase 2 and 3 trials, and the safety data are consistent with the broader integrated safety data analysis. The data show that naturally-aged TAK-003 had a well-tolerated reactogenicity and adverse events profile when administered in the second half of its clinical 24-month shelf-life and that it still elicited an immune response that persisted up to 6 months after the second dose against all four dengue serotypes, with no important safety risks identified during the trial.
Topics: Child; Adult; Humans; Aged; Dengue; Dengue Vaccines; Dengue Virus; Vaccines, Attenuated; Vaccines, Combined; Antibodies, Viral; Immunogenicity, Vaccine
PubMed: 37846724
DOI: 10.1080/21645515.2023.2254964 -
Vaccines Sep 2023(group A ; GAS), a Gram-positive coccal bacterium, poses a significant global disease burden, especially in low- and middle-income countries. Its manifestations can... (Review)
Review
(group A ; GAS), a Gram-positive coccal bacterium, poses a significant global disease burden, especially in low- and middle-income countries. Its manifestations can range from pharyngitis and skin infection to severe and aggressive diseases, such as necrotizing fasciitis and streptococcal toxic shock syndrome. At present, although GAS is still sensitive to penicillin, there are cases of treatment failure for GAS pharyngitis, and antibiotic therapy does not universally prevent subsequent disease. In addition to strengthening global molecular epidemiological surveillance and monitoring of antibiotic resistance, developing a safe and effective licensed vaccine against GAS would be the most effective way to broadly address GAS-related diseases. Over the past decades, the development of GAS vaccines has been stalled, mainly because of the wide genetic heterogeneity of GAS and the diverse autoimmune responses to GAS. With outbreaks of scarlet fever in various countries in recent years, accelerating the development of a safe and effective vaccine remains a high priority. When developing a GAS vaccine, many factors need to be considered, including the selection of antigen epitopes, avoidance of self-response, and vaccine coverage. Given the challenges in GAS vaccine development, this review describes the important virulence factors that induce disease by GAS infection and how this has influenced the progression of vaccine development efforts, focusing on several candidate vaccines that are further along in development.
PubMed: 37766186
DOI: 10.3390/vaccines11091510 -
Frontiers in Immunology 2023Crimean-Congo hemorrhagic fever (CCHF) is the most prevalent tick-borne viral disease affecting humans. The disease is life-threatening in many regions of the developing... (Review)
Review
Crimean-Congo hemorrhagic fever (CCHF) is the most prevalent tick-borne viral disease affecting humans. The disease is life-threatening in many regions of the developing world, including Africa, Asia, the Middle East, and Southern Europe. In line with the rapidly increasing disease prevalence, various vaccine strategies are under development. Despite a large number of potential vaccine candidates, there are no approved vaccines as of yet. This paper presents a detailed comparative analysis of current efforts to develop vaccines against CCHFV, limitations associated with current efforts, and future research directions.
Topics: Humans; Hemorrhagic Fever Virus, Crimean-Congo; Hemorrhagic Fever, Crimean; Africa; Asia; Vaccine Development
PubMed: 37753088
DOI: 10.3389/fimmu.2023.1238882 -
NPJ Vaccines Jun 2023Reference materials are critical in assay development for calibrating and assessing their suitability. The devasting nature of the COVID-19 pandemic and subsequent... (Review)
Review
Reference materials are critical in assay development for calibrating and assessing their suitability. The devasting nature of the COVID-19 pandemic and subsequent proliferation of vaccine platforms and technologies has meant that there is even a greater need for standards for immunoassay development, which are critical to assess and compare vaccines' responses. Equally important are the standards needed to control the vaccine manufacturing processes. Standardized vaccine characterization assays throughout process development are essential for a successful Chemistry, Manufacturing and Controls (CMC) strategy. In this perspective paper, we advocate for reference material incorporation into assays and their calibration to International Standards from preclinical vaccine development through control testing and provide insight into why this is necessary. We also provide information on the availability of WHO international antibody standards for CEPI-priority pathogens.
PubMed: 37391580
DOI: 10.1038/s41541-023-00692-0 -
Microbial Pathogenesis Jul 2023The monkeypox virus (MPOX) is an uncommon zoonotic illness brought on by an orthopoxvirus (OPXV). MPOX can occur with symptoms similar to smallpox. Since April 25, 2023,... (Review)
Review
The monkeypox virus (MPOX) is an uncommon zoonotic illness brought on by an orthopoxvirus (OPXV). MPOX can occur with symptoms similar to smallpox. Since April 25, 2023, 110 nations have reported 87,113 confirmed cases and 111 fatalities. Moreover, the outspread prevalence of MPOX in Africa and a current outbreak of MPOX in the U.S. have made it clear that naturally occurring zoonotic OPXV infections remain a public health concern. Existing vaccines, though they provide cross-protection to MPOX, are not specific for the causative virus, and their effectiveness in the light of the current multi-country outbreak is still to be verified. Furthermore, as a sequel of the eradication and cessation of smallpox vaccination for four decades, MPOX found a possibility to re-emerge, but with distinct characteristics. The World Health Organization (WHO) suggested that nations use affordable MPOX vaccines within a framework of coordinated clinical effectiveness and safety evaluations. Vaccines administered in the smallpox control program and conferred immunity against MPOX. Currently, vaccines approved by WHO for use against MPOX are replicating (ACAM2000), low replicating (LC16m8), and non-replicating (MVA-BN). Although vaccines are accessible, investigations have demonstrated that smallpox vaccination is approximately 85% efficient in inhibiting MPOX. In addition, developing new vaccine methods against MPOX can help prevent this infection. To recognize the most efficient vaccine, it is essential to assess effects, including reactogenicity, safety, cytotoxicity effect, and vaccine-associated side effects, especially for high-risk and vulnerable people. Recently, several orthopoxvirus vaccines have been produced and are being evaluated. Hence, this review aims to provide an overview of the efforts dedicated to several types of vaccine candidates with different strategies for MPOX, including inactivated, live-attenuated, virus-like particles (VLPs), recombinant protein, nucleic acid, and nanoparticle-based vaccines, which are being developed and launched.
Topics: Humans; Mpox (monkeypox); Smallpox; Vaccinia virus; Vaccination; Vaccine Development
PubMed: 37201635
DOI: 10.1016/j.micpath.2023.106156 -
Vaccine Oct 2023Hookworm, a parasitic infection, retains a considerable burden of disease, affecting the most underprivileged segments of the general population in endemic countries and...
Hookworm, a parasitic infection, retains a considerable burden of disease, affecting the most underprivileged segments of the general population in endemic countries and remains one of the leading causes of mild to severe anemia in Low and Middle Income Countries (LMICs), particularly in pregnancy and children under 5. Despite repeated large scale Preventive Chemotherapy (PC) interventions since more than 3 decades, there is broad consensus among scholars that elimination targets set in the newly launched NTD roadmap will require additional tools and interventions. Development of a vaccine could constitute a promising expansion of the existing arsenal against hookworm. Therefore, we have evaluated the biological and implementation feasibility of the vaccine development as well as the added value of such a novel tool. Based on pipeline landscaping and the current knowledge on key biological aspects of the pathogen and its interactions with the host, we found biological feasibility of development of a hookworm vaccine to be moderate. Also, our analysis on manufacturing and regulatory issues as well as potential uptake yielded moderate implementation feasibility. Modelling studies suggest a that introduction of a vaccine in parallel with ongoing integrated interventions (PC, WASH, shoe campaigns), could substantially reduce burden of disease in a cost - saving mode. Finally a set of actions are recommended that might impact positively the likelihood of timely development and introduction of a hookworm vaccine.
PubMed: 37863671
DOI: 10.1016/j.vaccine.2023.05.013