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The New England Journal of Medicine Feb 2024
Topics: Humans; Dengue; Dengue Vaccines; Dengue Virus; Vaccines, Attenuated
PubMed: 38294979
DOI: 10.1056/NEJMe2314240 -
Vaccine Aug 2020Shingles is a painful, blistering rash caused by reactivation of latent varicella-zoster virus (VZV) and most frequently occurs in elderly and immunocompromised...
Shingles is a painful, blistering rash caused by reactivation of latent varicella-zoster virus (VZV) and most frequently occurs in elderly and immunocompromised individuals. Currently, two approved vaccines for the prevention of shingles are on the market, a live attenuated virus vaccine ZOSTAVAX® (Merck & Co., Inc., Kenilworth, NJ, USA) and an AS01 adjuvanted subunit protein vaccine Shingrix™ (Glaxo Smith Kline, Rockville, MD, USA). Human clinical immunogenicity and vaccine efficacy data is available for these two benchmark vaccines, offering a unique opportunity for comparative analyses with novel vaccine platforms and animal model translatability studies. The studies presented here utilized non-human primates (NHP) to evaluate humoral and cellular immune response by three vaccine modalities: the new platform of lipid nanoparticle (LNP) formulated mRNA encoding VZV gE antigen (VZV gE mRNA/LNP) as compared with well-established platforms of live attenuated VZV (VZV LAV) and adjuvanted VZV gE subunit protein (VZV gE protein/adjuvant). The magnitude of response to vaccination with a single 100-200 μg mRNA dose or two 50 μg mRNA doses of VZV gE mRNA/LNP were comparable to two 50 μg protein doses of VZV gE protein/adjuvant, suggesting the VZV gE mRNA/LNP platform has the potential to elicit a robust immune response, and both modalities generated markedly higher responses than VZV LAV. Additionally, the slopes of decay for VZV-specific antibody titers were roughly similar across all three vaccines, indicating the magnitude of peak immunogenicity was the driving force in determining immune response longevity. Finally, vaccine-induced immunogenicity with VZV LAV and VZV gE protein/adjuvant in NHP closely resembled human clinical trials immune response data for ZOSTAVAX® and Shingrix™, helping to validate NHP as an appropriate preclinical model for evaluating these vaccines.
Topics: Animals; Antibodies, Viral; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; RNA, Messenger; Vaccines, Attenuated; Vaccines, Subunit; Viral Envelope Proteins
PubMed: 32703745
DOI: 10.1016/j.vaccine.2020.06.062 -
Clinical Infectious Diseases : An... Feb 2023An unmet medical need remains for an effective dengue tetravalent vaccine that can be administered irrespective of previous dengue exposure. TAK-003, a dengue... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
An unmet medical need remains for an effective dengue tetravalent vaccine that can be administered irrespective of previous dengue exposure. TAK-003, a dengue tetravalent vaccine, has demonstrated efficacy in an ongoing phase 3 trial in children and adolescents living in dengue-endemic areas, with an acceptable safety profile in both dengue-naive and dengue-exposed individuals.
METHODS
Safety findings are presented herein from an integrated analysis of data for healthy 4-60-year-olds from two phase 2 and three phase 3 double-blind, placebo-controlled clinical trials of TAK-003 (TAK-003, n = 14 627; placebo, n = 7167). Safety evaluation included analyses of postinjection reactogenicity, unsolicited adverse events (AEs), serious AEs (SAEs), and deaths. Subgroup analyses were performed by age group, baseline serostatus, and gender.
RESULTS
The most common local and systemic AEs were injection site pain (43% for TAK-003 and 26% for placebo) and headache (34% and 30%, respectively). Injection site AEs were mostly mild and resolved within 1-3 days. Unsolicited AEs and AEs leading to discontinuation occurred with similar frequency across both groups, while SAEs were fewer for TAK-003 recipients (6% vs 8% for placebo). Four of the 5 vaccine-related SAEs (which included hypersensitivity, dengue fever, and dengue hemorrhagic fever) occurred in the placebo group. No deaths were considered vaccine-related. Subgroup analyses showed no differences in safety by baseline serostatus or by gender, albeit analysis by age indicated greater local reactogenicity rates for adolescents (46% for TAK-003 and 28% for placebo) and adults (56% and 19%, respectively) than for children (37% and 25%, respectively).
CONCLUSIONS
No important safety risks were identified, and TAK-003 was well tolerated irrespective of age, gender, or baseline dengue serostatus in recipients aged 4-60 years.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Middle Aged; Young Adult; Antibodies, Viral; Dengue; Dengue Vaccines; Double-Blind Method; Vaccines, Attenuated
PubMed: 35639602
DOI: 10.1093/cid/ciac418 -
Science China. Life Sciences May 2020African swine fever (ASF) is a devastating infectious disease in swine that is severely threatening the global pig industry. An efficacious vaccine is urgently required....
African swine fever (ASF) is a devastating infectious disease in swine that is severely threatening the global pig industry. An efficacious vaccine is urgently required. Here, we used the Chinese ASFV HLJ/18 as a backbone and generated a series of gene-deleted viruses. The virulence, immunogenicity, safety, and protective efficacy evaluation in specific-pathogen-free pigs, commercial pigs, and pregnant sows indicated that one virus, namely HLJ/18-7GD, which has seven genes deleted, is fully attenuated in pigs, cannot convert to the virulent strain, and provides complete protection of pigs against lethal ASFV challenge. Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV, and as such is expected to play an important role in controlling the spread of ASFV.
Topics: African Swine Fever; African Swine Fever Virus; Animals; Gene Deletion; Genome, Viral; Humans; Recombinant Proteins; Sequence Analysis, DNA; Swine; Vaccines, Attenuated; Viral Proteins; Viral Vaccines; Virulence
PubMed: 32124180
DOI: 10.1007/s11427-020-1657-9 -
Expert Review of Vaccines Dec 2022Whole cell and acellular pertussis vaccines have been very effective in decreasing the deaths of neonates and infants from . Despite high vaccine coverage worldwide,... (Review)
Review
INTRODUCTION
Whole cell and acellular pertussis vaccines have been very effective in decreasing the deaths of neonates and infants from . Despite high vaccine coverage worldwide, pertussis remains one of the most common vaccine-preventable diseases, thus suggesting that new pertussis vaccination strategies are needed. Several candidates are currently under development, such as acellular pertussis vaccines that use genetically detoxified pertussis toxin, acellular pertussis vaccines delivered with new adjuvants or new delivery systems, or an intranasally delivered, live attenuated vaccine.
AREAS COVERED
This review discusses the different possibilities for improving current pertussis vaccines and the present state of knowledge on the pertussis vaccine candidates under development.
EXPERT OPINION
Until there is a safe, effective, and affordable alternative to the two types of existing vaccines, we should maintain sufficient childhood coverage and increase the vaccination of pregnant women, adolescents, and young adults.
Topics: Pregnancy; Adolescent; Infant; Infant, Newborn; Young Adult; Female; Humans; Child; Whooping Cough; Bordetella pertussis; Vaccine-Preventable Diseases; Vaccination; Vaccines, Attenuated
PubMed: 36400443
DOI: 10.1080/14760584.2022.2149499 -
Cold Spring Harbor Perspectives in... Sep 2021Live attenuated, cold-adapted influenza vaccines exhibit several desirable characteristics, including the induction of systemic, mucosal, and cell-mediated immunity... (Review)
Review
Live attenuated, cold-adapted influenza vaccines exhibit several desirable characteristics, including the induction of systemic, mucosal, and cell-mediated immunity resulting in breadth of protection, ease of administration, and yield. Seasonal live attenuated influenza vaccines (LAIVs) were developed in the United States and Russia and have been used in several countries. In the last decade, following the incorporation of the 2009 pandemic H1N1 strain, the performance of both LAIVs has been variable and the U.S.-backbone LAIV was less effective than the corresponding inactivated influenza vaccines. The cause appears to be reduced replicative fitness of some H1N1pdm09 viruses, indicating a need for careful selection of strains included in multivalent LAIV formulations. Assays are now being implemented to select optimal strains. An improved understanding of the determinants of replicative fitness of vaccine strains and of vaccine effectiveness of LAIVs is needed for public health systems to take full advantage of these valuable vaccines.
Topics: Humans; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Russia; United States; Vaccine Efficacy; Vaccines, Attenuated
PubMed: 32253347
DOI: 10.1101/cshperspect.a038653 -
Expert Opinion on Biological Therapy Mar 2022Rotavirus is the primary cause of severe acute gastroenteritis among children under the age of five globally, leading to 128,500 to 215,000 vaccine-preventable deaths... (Review)
Review
INTRODUCTION
Rotavirus is the primary cause of severe acute gastroenteritis among children under the age of five globally, leading to 128,500 to 215,000 vaccine-preventable deaths annually. There are six licensed oral, live-attenuated rotavirus vaccines: four vaccines pre-qualified for global use by WHO, and two country-specific vaccines. Expansion of rotavirus vaccines into national immunization programs worldwide has led to a 59% decrease in rotavirus hospitalizations and 36% decrease in diarrhea deaths due to rotavirus in vaccine-introducing countries.
AREAS COVERED
This review describes the current rotavirus vaccines in use, global coverage, vaccine efficacy from clinical trials, and vaccine effectiveness and impact from post-licensure evaluations. Vaccine safety, particularly as it relates to the risk of intussusception, is also summarized. Additionally, an overview of candidate vaccines in the pipeline is provided.
EXPERT OPINION
Considerable evidence over the past decade has demonstrated high effectiveness (80-90%) of rotavirus vaccines at preventing severe rotavirus disease in high-income countries, although the effectiveness has been lower (40-70%) in low-to-middle-income countries. Surveillance and research should continue to explore modifiable factors that influence vaccine effectiveness, strengthen data to better evaluate newer rotavirus vaccines, and aid in the development of future vaccines that can overcome the limitations of current vaccines.
Topics: Child; Diarrhea; Humans; Immunization Programs; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 34482790
DOI: 10.1080/14712598.2021.1977279 -
Advances in Experimental Medicine and... 2023The hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection associated damage...
The hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals, two of them were tested in human and evidenced to be well-tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin (HEV 239 vaccine), was licensed in China and launched in 2012.
Topics: Pregnancy; Adult; Animals; Aged; Humans; Female; Hepatitis E; Capsid Proteins; China; Sedentary Behavior; Vaccines, Attenuated
PubMed: 37223870
DOI: 10.1007/978-981-99-1304-6_16 -
Vaccine Feb 2020Cholera remains a major global public health problem that is primarily linked to insufficient access to safe water and proper sanitation. Oral Cholera Vaccine (OCV) has... (Review)
Review
Cholera remains a major global public health problem that is primarily linked to insufficient access to safe water and proper sanitation. Oral Cholera Vaccine (OCV) has been recommended as an additional public health tool along with WASH in cholera endemic countries and in areas at risk for outbreaks. The new generation OCV is safe and offers good protection in older children and adults while limited protection in younger children less than five years of age has been observed. The combination of direct vaccine protection and vaccine herd immunity effects makes OCV highly cost-effective and, therefore, attractive for use in developing countries. Additionally, in recent studies OCV was safe in pregnant women, supporting its use in pregnant women in cholera endemic countries. However, knowledge need to be developed for current vaccines for their prolonged duration of protection and vaccines need improvements for better immune response in younger children. A single dose vaccination regimen would be more cost-effective and easier to deliver. Recent approaches have focused on designing genetically attenuated cholera strains for use in single-dose cholera vaccines. The global demand for OCV has been boosted by the WHO recommendation to use OCV and is driven largely by epidemics and outbreaks and has been increasing due to the availability of cheaper easy-to-use vaccines, feasibility of mass OCV vaccination campaigns, demonstration of protection to underserved population in precarious situations, and vaccine costs being borne by Gavi (Vaccine Alliance). For rapid access in emergency and equitable distribution of OCV in cholera-endemic low-income countries, a global OCV stockpile was established in 2013 with support from the Global Alliance for Vaccines and Immunization. The three WHO-prequalified vaccines are Dukoral®, Shanchol™, Euvichol® (and Euvichol® Plus presentation), the latter two being included in the stockpile.
Topics: Administration, Oral; Adult; Child; Cholera; Cholera Vaccines; Disease Outbreaks; Female; Humans; Pregnancy; Vaccination; Vaccines, Attenuated
PubMed: 31879125
DOI: 10.1016/j.vaccine.2019.12.011 -
Current Rheumatology Reports May 2020Several biologic drugs are available for treatment of immune-mediated diseases, and the number of children treated with biologics is increasing. This review summarises... (Review)
Review
PURPOSE OF REVIEW
Several biologic drugs are available for treatment of immune-mediated diseases, and the number of children treated with biologics is increasing. This review summarises current knowledge about the safety and immunogenicity of vaccines in children treated with biologic therapy.
RECENT FINDINGS
A recent retrospective, multicentre study reported that the booster dose of live-attenuated vaccine (MMR/V) was safe for patients with rheumatic diseases treated with biologic therapy. Recent publications revealed that immunogenicity of vaccines in children treated with biologics was lower than in the healthy population, especially on long-term follow-up. Children treated with biologic therapy are at greater danger of infections, compared to the healthy population. Therefore, they should be vaccinated according to national guidelines. Regardless of the therapy, non-live vaccines are recommended. However, it is common practice to advise postponing vaccination with live-attenuated vaccines in children while they are on immunosuppressive therapy. Newly published data suggest that booster dose MMR/V is safe for children treated with biologic therapy.
Topics: Biological Products; Child; Humans; Immunization, Secondary; Immunogenicity, Vaccine; Measles-Mumps-Rubella Vaccine; Multicenter Studies as Topic; Retrospective Studies; Rheumatic Diseases; Vaccination; Vaccines, Attenuated
PubMed: 32436130
DOI: 10.1007/s11926-020-00905-8