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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 -
Bundesgesundheitsblatt,... Jan 2020Dengue, the most common arbovirus, represents an increasingly significant cause of morbidity worldwide, including in travelers. After decades of research, the first... (Review)
Review
Dengue, the most common arbovirus, represents an increasingly significant cause of morbidity worldwide, including in travelers. After decades of research, the first dengue vaccine was licensed in 2015: CYD-TDV, a tetravalent live attenuated vaccine with a yellow fever vaccine backbone. Recent analyses have shown that vaccine performance is dependent on serostatus. In those who have had a previous dengue infection, i.e., who are seropositive, the efficacy is high and the vaccine is safe. However, in seronegative vaccinees, approximately 3 years after vaccination the vaccine increases the risk of developing severe dengue when the individual experiences a natural dengue infection.The World Health Organization recommends that this vaccine be administered only to seropositive individuals. Current efforts are underway to develop rapid diagnostic tests to facilitate prevaccination screening. Two second-generation dengue vaccine candidates, both also live attenuated recombinant vaccines in late-stage development, may not present the same limitations because of differences in the backbone used, but results of phase 3 trials need to be available before firm conclusions can be drawn.Dengue is increasingly frequent in travelers, but the only licensed dengue vaccine to date can be used only in seropositive individuals. However, the vast majority of travelers are seronegative. Furthermore, the primary series of three doses given 6 months apart renders this vaccine difficult in the travel medicine context.
Topics: Antibodies, Viral; Dengue; Dengue Vaccines; Germany; Humans; Vaccination; Vaccines, Attenuated
PubMed: 31784763
DOI: 10.1007/s00103-019-03060-3 -
Current Opinion in Virology Apr 2017Respiratory syncytial virus (RSV) is an important and ubiquitous respiratory pathogen for which no vaccine is available notwithstanding more than 50 years of effort. It... (Review)
Review
Respiratory syncytial virus (RSV) is an important and ubiquitous respiratory pathogen for which no vaccine is available notwithstanding more than 50 years of effort. It causes the most severe disease at the extremes of age and in settings of immunodeficiency. Although RSV is susceptible to neutralizing antibody, it has evolved multiple mechanisms of immune evasion allowing it to repeatedly infect people despite relatively little genetic diversity. Recent breakthroughs in determining the structure and antigenic content of the fusion (F) glycoprotein in its metastable untriggered prefusion form (pre-F) and the stable rearranged postfusion form (post-F) have yielded vaccine strategies that can induce potent neutralizing antibody responses and effectively boost pre-existing neutralizing activity. In parallel, novel live-attenuated and chimeric virus vaccine candidates and other novel approaches to deliver vaccine antigens have been developed. These events and activities have aroused optimism and a robust pipeline of potential vaccine products that promise to provide a means to reduce the public health burden of RSV infection.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Drug Discovery; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Vaccines, Attenuated; Vaccines, Synthetic; Viral Fusion Proteins
PubMed: 28525878
DOI: 10.1016/j.coviro.2017.03.012 -
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 -
Virology May 2015Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared... (Review)
Review
Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed.
Topics: Clinical Trials as Topic; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Vaccines, Attenuated; Viral Vaccines; Virus Diseases
PubMed: 25864107
DOI: 10.1016/j.virol.2015.03.032 -
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