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Biologicals : Journal of the... Sep 2014Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield... (Review)
Review
Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. This review covers key concepts in understanding the causes and mechanisms of vaccine instability including (1) the complex and delicate nature of antigen structures (e.g., viruses, proteins, carbohydrates, protein-carbohydrate conjugates, etc.), (2) use of adjuvants to further enhance immune responses, (3) development of physicochemical and biological assays to assess vaccine integrity and potency, and (4) stabilization strategies to protect vaccine antigens and adjuvants (and their interactions) during storage. Despite these challenges, vaccines can usually be sufficiently stabilized for use as medicines through a combination of formulation approaches combined with maintenance of an efficient cold chain (manufacturing, distribution, storage and administration). Several illustrative case studies are described regarding mechanisms of vaccine instability along with formulation approaches for stabilization within the vaccine cold chain. These include live, attenuated (measles, polio) and inactivated (influenza, polio) viral vaccines as well as recombinant protein (hepatitis B) vaccines.
Topics: Adjuvants, Immunologic; Animals; Antigens; Chemistry, Pharmaceutical; Cold Temperature; Drug Stability; Drug Storage; Hepatitis B Vaccines; Humans; Influenza Vaccines; Measles Vaccine; Poliovirus Vaccines; Vaccines
PubMed: 24996452
DOI: 10.1016/j.biologicals.2014.05.007 -
Transactions of the Royal Society of... Jan 2015WHO recommends delaying measles vaccination (MV) until maternal antibody has waned. However, early MV may improve child survival by reducing mortality from conditions... (Review)
Review
WHO recommends delaying measles vaccination (MV) until maternal antibody has waned. However, early MV may improve child survival by reducing mortality from conditions other than measles infection. We tested whether early MV improves child survival compared with later MV. We found 43 studies comparing measles-vaccinated and measles-unvaccinated children; however, only 16 studies had specific information that MV had been provided at 4-13 months of age, many before 9 months of age. In the 10 best studies (4 randomized trials and 6 observational studies) control children did not receive MV during follow-up. In eight of these studies the vaccine efficacy against death (VED) was 60% or more. In four studies with information on MV provided both before and after 12 months of age, the all-cause mortality reduction was significantly larger for children vaccinated in infancy (VED=74%; 95% CI 51-86%) than for children vaccinated after 12 months of age (VED=29%; CI 8-46%). Prevention of measles explained little of the reduction in mortality. In five studies with information on measles infection, VED was 67% (51-78%) and when measles deaths were excluded, VED was only reduced to 65% (47-77%). One natural experiment compared MV at 4-8 months versus MV at 9-11 months of age and found significantly lower all-cause mortality with early vaccination, the difference being 39% (8-60%). Child mortality may be reduced if MV is given earlier than currently recommended by international organizations.
Topics: Antibodies, Viral; Child, Preschool; Humans; Immunity, Maternally-Acquired; Immunization Schedule; Immunization, Secondary; Infant; Measles; Measles Vaccine; Survival Analysis; Vaccination
PubMed: 25573106
DOI: 10.1093/trstmh/tru174 -
Vaccine May 2019Despite increasing global measles vaccination coverage, progress toward measles elimination has slowed in recent years. In China, children receive a measles-containing...
Despite increasing global measles vaccination coverage, progress toward measles elimination has slowed in recent years. In China, children receive a measles-containing vaccine (MCV) at 8 months, 18-24 months, and some urban areas offer a third dose at age 4-6 years. However, substantial measles cases in Tianjin, China, occur among individuals who have received multiple MCV doses. This study describes the vaccination history of measles cases 8 months - 19 years old. Data came from measles cases in Tianjin's reportable disease surveillance system (2009-2013), and from a case control study (2011-2015). Twenty-nine percent of those in the surveillance dataset and 54.4% of those in the case series received at least one dose of MCV. The minimum and median time-to-diagnosis since vaccination revealed an increase in time since vaccination for incremental doses. Considerable measles cases in Tianjin occur in vaccinated children, and further research is needed to understand the reasons for vaccine failure.
Topics: Adolescent; Case-Control Studies; Child; Child, Preschool; China; Disease Outbreaks; Epidemiological Monitoring; Female; Humans; Immunization Schedule; Infant; Male; Measles; Measles Vaccine; Treatment Failure; Vaccination Coverage; Young Adult
PubMed: 31078327
DOI: 10.1016/j.vaccine.2019.05.005 -
The Pan African Medical Journal 2020The African Region is committed to measles elimination by 2020 but coverage with the first dose of measles-containing vaccine was only 70% in 2017. Several obstacles to... (Review)
Review
The African Region is committed to measles elimination by 2020 but coverage with the first dose of measles-containing vaccine was only 70% in 2017. Several obstacles to achieving high coverage with measles and rubella vaccines exist, some of which could be overcome with new vaccine delivery technologies. Microarray array patches (MAPs) are single-dose devices used for transcutaneous administration of molecules, including inactivated or attenuated vaccines, that penetrate the outer stratum corneum of the skin, delivering antigens to the epidermis or dermis. MAPs to deliver measles and rubella vaccines have the potential to be a transformative technology to achieve elimination goals in the African Region. MAPs for measles and rubella vaccination have been shown to be safe, immunogenic and thermostable in preclinical studies but results of clinical studies in humans have not yet been published. This review summarizes the current state of knowledge of measles and rubella MAPs, their potential advantages for immunization programs in the African Region, and some of the challenges that must be overcome before measles and rubella MAPs are available for widespread use.
Topics: Administration, Cutaneous; Africa; Humans; Immunization Programs; Measles; Measles Vaccine; Microtechnology; Patient Acceptance of Health Care; Rubella; Rubella Vaccine; Transdermal Patch; Vaccination Coverage
PubMed: 32373254
DOI: 10.11604/pamj.supp.2020.35.1.19753 -
Emerging Infectious Diseases Nov 2020Controlling measles outbreaks in the country of Georgia and throughout Europe is crucial for achieving the measles elimination goal for the World Health Organization's...
Controlling measles outbreaks in the country of Georgia and throughout Europe is crucial for achieving the measles elimination goal for the World Health Organization's European Region. However, large-scale measles outbreaks occurred in Georgia during 2013-2015 and 2017-2018. The epidemiology of these outbreaks indicates widespread circulation and genetic diversity of measles viruses and reveals persistent gaps in population immunity across a wide age range that have not been sufficiently addressed thus far. Historic problems and recent challenges with the immunization program contributed to outbreaks. Addressing population susceptibility across all age groups is needed urgently. However, conducting large-scale mass immunization campaigns under the current health system is not feasible, so more selective response strategies are being implemented. Lessons from the measles outbreaks in Georgia could be useful for other countries that have immunization programs facing challenges related to health-system transitions and the presence of age cohorts with historically low immunization coverage.
Topics: Adolescent; Adult; Child; Child, Preschool; Disease Eradication; Disease Outbreaks; Female; Georgia (Republic); Humans; Immunization Programs; Infant; Infant, Newborn; Male; Measles; Measles Vaccine; Middle Aged; Vaccination; Vaccination Coverage; Young Adult
PubMed: 33079037
DOI: 10.3201/eid2611.200259 -
Vaccine Apr 2022To determine whether children aged 4-7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency...
OBJECTIVES
To determine whether children aged 4-7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD.
METHODS
The study included children born between 1995-2012, aged 4-7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions.
RESULTS
The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58-1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63-2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80-1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59-1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD.
CONCLUSION
Children with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.
Topics: Autism Spectrum Disorder; Chickenpox Vaccine; Child; Fever; Humans; Infant; Measles; Measles Vaccine; Measles-Mumps-Rubella Vaccine; Seizures, Febrile; Vaccines, Combined; Whooping Cough
PubMed: 35315325
DOI: 10.1016/j.vaccine.2022.03.031 -
Science (New York, N.Y.) May 2019All World Health Organization regions have set measles elimination goals. We find that as countries progress toward these goals, they undergo predictable changes in the...
All World Health Organization regions have set measles elimination goals. We find that as countries progress toward these goals, they undergo predictable changes in the size and frequency of measles outbreaks. A country's position on this "canonical path" is driven by both measles control activities and demographic factors, which combine to change the effective size of the measles-susceptible population, thereby driving the country through theoretically established dynamic regimes. Further, position on the path to elimination provides critical information for guiding vaccination efforts, such as the age profile of susceptibility, that could only otherwise be obtained through costly field studies or sophisticated analysis. Equipped with this information, countries can gain insight into their current and future measles epidemiology and select appropriate strategies to more quickly achieve elimination goals.
Topics: Child; Demography; Disease Eradication; Disease Susceptibility; Global Health; Humans; Measles; Measles Vaccine; Vaccination; World Health Organization
PubMed: 31073065
DOI: 10.1126/science.aau6299 -
Revista Chilena de Pediatria Jun 2019Measles is still a major cause of child morbidity and mortality. In recent years, it has become a global public health problem, attributed to low vaccination coverage... (Review)
Review
Measles is still a major cause of child morbidity and mortality. In recent years, it has become a global public health problem, attributed to low vaccination coverage observed in different countries. In order to control it, a highly effective live virus vaccine is available, which was used for the first time in Chile in 1964, covering practically the whole country in a short period of time. This was the first world experience, which was later imitated by other countries leading to a significant drop in mor bidity and mortality rates. Its effectiveness has been amply demonstrated, but it requires coverage maintenance higher than 95%. In Chile, minor endemic situation persisted until 1993. In recent years, there have been some reduced outbreaks and sporadic cases linked to contacts with imported cases, however, according to recent data, measles is now circulating in more than 160 countries at an unprecedented spread level, where infected travelers are the main vehicle of transmission. In Chile, the Ministry of Health has decided to strengthen and update the vaccination of susceptible groups, especially travelers. This update reviews historical aspects and current information on this re-emer ging disease, showing its high epidemiological impact on the pediatric and adult population globally.
Topics: Adult; Child; Chile; Disease Outbreaks; Humans; Measles; Measles Vaccine; Public Health; Vaccination
PubMed: 31344184
DOI: 10.32641/rchped.v90i3.1231 -
The Pan African Medical Journal 2020The recent setbacks in efforts to achieve measles elimination goals are alarming. To reverse the current trends, it is imperative that the global health community...
The recent setbacks in efforts to achieve measles elimination goals are alarming. To reverse the current trends, it is imperative that the global health community urgently intensify efforts and make resource commitments to implement evidence-based elimination strategies fully, including supporting research and innovations. The Immunization Agenda 2030: A Global Strategy to Leave No One Behind (IA2030) is the new global guidance document that builds on lessons learned and progress made toward the GVAP goals, includes research and innovation as a core strategic priority, and identifies measles as a "tracer" for improving immunisation services and strengthening primary health care systems. To achieve vaccination coverage and equity targets that leave no one behind, and accelerate progress toward disease eradication and elimination goals, sustained and predictable investments are needed for the identified research and innovations priorities for the new decade.
Topics: Disease Eradication; Disease Outbreaks; Fund Raising; Global Health; Humans; Immunization; Immunization Programs; Incidence; Inventions; Investments; Measles; Measles Vaccine; Vaccination Coverage
PubMed: 32373266
DOI: 10.11604/pamj.supp.2020.35.1.21740 -
Frontiers in Public Health 2022Measles and rubella microarray patches (MR-MAPs) are critical in achieving measles and rubella eradication, a goal highly unlikely to meet with current vaccines... (Review)
Review
Measles and rubella microarray patches (MR-MAPs) are critical in achieving measles and rubella eradication, a goal highly unlikely to meet with current vaccines presentations. With low commercial incentive to MAP developers, limited and uncertain funding, the need for investment in a novel manufacturing facility, and remaining questions about the source of antigen, product demand, and regulatory pathway, MR-MAPs are unlikely to be prequalified by WHO and ready for use before 2033. This article describes the current progress of MR-MAPs, highlights challenges and opportunities pertinent to MR-MAPs manufacturing, regulatory approval, creating demand, and timelines to licensure. It also describes activities that are being undertaken by multiple partners to incentivise investment in and accelerate the development of MR-MAPs.
Topics: Humans; Measles; Measles Vaccine; Rubella; Rubella Vaccine
PubMed: 35309224
DOI: 10.3389/fpubh.2022.809675