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Viral Immunology Mar 2018Measles remains an important cause of child morbidity and mortality worldwide despite the availability of a safe and efficacious vaccine. The current measles virus (MeV)... (Review)
Review
Measles remains an important cause of child morbidity and mortality worldwide despite the availability of a safe and efficacious vaccine. The current measles virus (MeV) vaccine was developed empirically by attenuation of wild-type (WT) MeV by in vitro passage in human and chicken cells and licensed in 1963. Additional passages led to further attenuation and the successful vaccine strains in widespread use today. Attenuation is associated with decreased replication in lymphoid tissue, but the molecular basis for this restriction has not been identified. The immune response is age dependent, inhibited by maternal antibody (Ab) and involves induction of both Ab and T cell responses that resemble the responses to WT MeV infection, but are lower in magnitude. Protective immunity is correlated with levels of neutralizing Ab, but the actual immunologic determinants of protection are not known. Because measles is highly transmissible, control requires high levels of population immunity. Delivery of the two doses of vaccine needed to achieve >90% immunity is accomplished by routine immunization of infants at 9-15 months of age followed by a second dose delivered before school entry or by periodic mass vaccination campaigns. Because delivery by injection creates hurdles to sustained high coverage, there are efforts to deliver MeV vaccine by inhalation. In addition, the safety record for the vaccine combined with advances in reverse genetics for negative strand viruses has expanded proposed uses for recombinant versions of measles vaccine as vectors for immunization against other infections and as oncolytic agents for a variety of tumors.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Disease Transmission, Infectious; Drug Discovery; Humans; Immunization Schedule; Measles; Measles Vaccine; Measles virus; Serial Passage; Technology, Pharmaceutical; Vaccines, Attenuated
PubMed: 29256824
DOI: 10.1089/vim.2017.0143 -
Future Microbiology 2015Live attenuated oral polio vaccine (OPV) and inactivated polio vaccine (IPV) are the tools being used to achieve eradication of wild polio virus. Because OPV can rarely... (Review)
Review
Live attenuated oral polio vaccine (OPV) and inactivated polio vaccine (IPV) are the tools being used to achieve eradication of wild polio virus. Because OPV can rarely cause paralysis and generate revertant polio strains, IPV will have to replace OPV after eradication of wild polio virus is certified to sustain eradication of all polioviruses. However, uncertainties remain related to IPV's ability to induce intestinal immunity in populations where fecal-oral transmission is predominant. Although substantial effectiveness and safety data exist on the use and delivery of OPV and IPV, several new research initiatives are currently underway to fill specific knowledge gaps to inform future vaccination policies that would assure polio is eradicated and eradication is maintained.
Topics: History, 20th Century; History, 21st Century; Humans; Poliomyelitis; Poliovirus Vaccines; Vaccination; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 25824845
DOI: 10.2217/fmb.15.19 -
Expert Review of Vaccines Dec 2017Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing... (Review)
Review
Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines' efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms.
Topics: Chickenpox; Chickenpox Vaccine; Clinical Trials as Topic; Drug Approval; Drug Discovery; Herpes Zoster; Herpes Zoster Vaccine; Humans; Product Surveillance, Postmarketing; Treatment Outcome; Vaccines, Attenuated; Vaccines, Subunit
PubMed: 29047317
DOI: 10.1080/14760584.2017.1394843 -
Human Vaccines & Immunotherapeutics 2019Dengue is the world's most prevalent and important arboviral disease. More than 50% of the world's population lives at daily risk of infection and it is estimated more... (Review)
Review
Dengue is the world's most prevalent and important arboviral disease. More than 50% of the world's population lives at daily risk of infection and it is estimated more than 95 million people a year seek medical care following infection. Severe disease can manifest as plasma leakage and potential for clinically significant hemorrhage, shock, and death. Treatment is supportive and there is currently no licensed anti-dengue virus prophylactic or therapeutic compound. A single dengue vaccine, Sanofi Pasteur's Dengvaxia®, has been licensed in 20 countries but uptake has been poor. A safety signal in dengue seronegative vaccine recipients stimulated an international re-look at the vaccine performance profile, new World Health Organization recommendations for use, and controversy in the Philippines involving the government, regulatory agencies, Sanofi Pasteur, clinicians responsible for testing and administering the vaccine, and the parents of vaccinated children. In this review, we provide an overview of Dengvaxia's® development and discuss what has been learned about product performance since its licensure.
Topics: Animals; Dengue; Dengue Vaccines; Dengue Virus; Humans; Immunogenicity, Vaccine; Licensure; Philippines; Vaccination; Vaccines, Attenuated; World Health Organization
PubMed: 31589551
DOI: 10.1080/21645515.2019.1658503 -
Cell Host & Microbe May 2020The live-attenuated oral poliovirus vaccine (OPV or Sabin vaccine) replicates in gut-associated tissues, eliciting mucosa and systemic immunity. OPV protects from...
The live-attenuated oral poliovirus vaccine (OPV or Sabin vaccine) replicates in gut-associated tissues, eliciting mucosa and systemic immunity. OPV protects from disease and limits poliovirus spread. Accordingly, vaccination with OPV is the primary strategy used to end the circulation of all polioviruses. However, the ability of OPV to regain replication fitness and establish new epidemics represents a significant risk of polio re-emergence should immunization cease. Here, we report the development of a poliovirus type 2 vaccine strain (nOPV2) that is genetically more stable and less likely to regain virulence than the original Sabin2 strain. We introduced modifications within at the 5' untranslated region of the Sabin2 genome to stabilize attenuation determinants, 2C coding region to prevent recombination, and 3D polymerase to limit viral adaptability. Prior work established that nOPV2 is immunogenic in preclinical and clinical studies, and thus may enable complete poliovirus eradication.
Topics: Adult; Animals; Chlorocebus aethiops; Disease Models, Animal; Female; Genetic Engineering; HeLa Cells; Humans; Immunogenicity, Vaccine; Male; Mice; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; RNA, Viral; RNA-Dependent RNA Polymerase; Recombination, Genetic; Vaccination; Vaccines, Attenuated; Vero Cells; Virulence
PubMed: 32330425
DOI: 10.1016/j.chom.2020.04.003 -
Human Vaccines & Immunotherapeutics 2015Measles was an inevitable infection during the human development with substantial degree of morbidity and mortality. The severity of measles virus (MV) infection was... (Review)
Review
Measles was an inevitable infection during the human development with substantial degree of morbidity and mortality. The severity of measles virus (MV) infection was largely contained by the development of a live attenuated vaccine that was introduced into the vaccination programs. However, all efforts to eradicate the disease failed and continued to annually result in significant deaths. The development of molecular biology techniques allowed the rescue of MV from cDNA that enabled important insights into a variety of aspects of the biology of the virus and its pathogenesis. Subsequently these technologies facilitated the development of novel vaccine candidates that induce immunity against measles and other pathogens. Based on the promising prospective, the use of MV as a recombinant vaccine and a therapeutic vector is addressed.
Topics: Drug Carriers; Genetic Vectors; Humans; Measles; Measles Vaccine; Measles virus; Oncolytic Virotherapy; Vaccines, Attenuated; Vaccines, Synthetic
PubMed: 25483511
DOI: 10.4161/hv.34298 -
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 -
Frontiers in Immunology 2022Dengue is the most common arboviral disease caused by one of four distinct but closely related dengue viruses (DENV) and places significant economic and public health... (Review)
Review
Dengue is the most common arboviral disease caused by one of four distinct but closely related dengue viruses (DENV) and places significant economic and public health burdens in the endemic areas. A dengue vaccine will be important in advancing disease control. However, the effort has been challenged by the requirement to induce effective protection against all four DENV serotypes and the potential adverse effect due to the phenomenon that partial immunity to DENV may worsen the symptoms upon subsequent heterotypic infection. Currently, the most advanced dengue vaccines are all tetravalent and based on recombinant live attenuated viruses. CYD-TDV, developed by Sanofi Pasteur, has been approved but is limited for use in individuals with prior dengue infection. Two other tetravalent live attenuated vaccine candidates: TAK-003 by Takeda and TV003 by National Institute of Allergy and Infectious Diseases, have completed phase 3 and phase 2 clinical trials, respectively. This review focuses on the designs and evaluation of TAK-003 and TV003 vaccine candidates in humans in comparison to the licensed CYD-TDV vaccine. We highlight specific lessons from existing studies and challenges that must be overcome in order to develop a dengue vaccine that confers effective and balanced protection against all four DENV serotypes but with minimal adverse effects.
Topics: Antibodies, Viral; Dengue; Dengue Vaccines; Drug-Related Side Effects and Adverse Reactions; Humans; Vaccines, Attenuated
PubMed: 35281026
DOI: 10.3389/fimmu.2022.840104 -
Scandinavian Journal of Infectious... 2008Two live attenuated oral rotavirus vaccines were licensed in 2006 for prevention of severe acute gastroenteritis in children: Rotarix (GSK), a human rotavirus vaccine... (Review)
Review
Two live attenuated oral rotavirus vaccines were licensed in 2006 for prevention of severe acute gastroenteritis in children: Rotarix (GSK), a human rotavirus vaccine with G1P[8] serotype characteristics and RotaTeq (Merck), a bovine-human reassortant vaccine expressing human G1-4 and P[8] antigens. In prelicensure trials both vaccines showed high efficacy against severe RV gastroenteritis, low reactogenicity and no increased risk for intussusception (IS) (Ruiz-Palacios et al., 2006; Vesikari et al., 2006). Both vaccines have now been distributed in millions of doses. Post-marketing data have not shown any gross signal for IS with either vaccine, but further data and analyses are required for final conclusion on safety of these vaccines.
Topics: Animals; Cattle; Clinical Trials as Topic; Gastroenteritis; Humans; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Treatment Outcome; Vaccination; Vaccines, Attenuated
PubMed: 19086243
DOI: 10.1080/00365540802040570 -
Trends in Microbiology Jan 2018Genetic engineering now enables the design of live viral vaccines that are potentially transmissible. Some designs merely modify a single viral genome to improve on the... (Review)
Review
Genetic engineering now enables the design of live viral vaccines that are potentially transmissible. Some designs merely modify a single viral genome to improve on the age-old method of attenuation whereas other designs create chimeras of viral genomes. Transmission has the benefit of increasing herd immunity above that achieved by direct vaccination alone but also increases the opportunity for vaccine evolution, which typically undermines vaccine utility. Different designs have different epidemiological consequences but also experience different evolution. Approaches that integrate vaccine engineering with an understanding of evolution and epidemiology will reap the greatest benefit from vaccine transmission.
Topics: Communicable Disease Control; Cross Reactions; Disease Eradication; Epidemiology; Genetic Engineering; Humans; Immunity, Herd; Models, Theoretical; Vaccination; Vaccines, Attenuated; Vaccines, Synthetic; Viral Vaccines; Viruses
PubMed: 29033339
DOI: 10.1016/j.tim.2017.09.007