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Proceedings of the National Academy of... Oct 2023As SARS-CoV-2 variants of concern (VoCs) that evade immunity continue to emerge, next-generation adaptable COVID-19 vaccines which protect the respiratory tract and...
As SARS-CoV-2 variants of concern (VoCs) that evade immunity continue to emerge, next-generation adaptable COVID-19 vaccines which protect the respiratory tract and provide broader, more effective, and durable protection are urgently needed. Here, we have developed one such approach, a highly efficacious, intranasally delivered, trivalent measles-mumps-SARS-CoV-2 spike (S) protein (MMS) vaccine candidate that induces robust systemic and mucosal immunity with broad protection. This vaccine candidate is based on three components of the MMR vaccine, a measles virus Edmonston and the two mumps virus strains [Jeryl Lynn 1 (JL1) and JL2] that are known to provide safe, effective, and long-lasting protective immunity. The six proline-stabilized prefusion S protein (preS-6P) genes for ancestral SARS-CoV-2 WA1 and two important SARS-CoV-2 VoCs (Delta and Omicron BA.1) were each inserted into one of these three viruses which were then combined into a trivalent "MMS" candidate vaccine. Intranasal immunization of MMS in IFNAR1 mice induced a strong SARS-CoV-2-specific serum IgG response, cross-variant neutralizing antibodies, mucosal IgA, and systemic and tissue-resident T cells. Immunization of golden Syrian hamsters with MMS vaccine induced similarly high levels of antibodies that efficiently neutralized SARS-CoV-2 VoCs and provided broad and complete protection against challenge with any of these VoCs. This MMS vaccine is an efficacious, broadly protective next-generation COVID-19 vaccine candidate, which is readily adaptable to new variants, built on a platform with a 50-y safety record that also protects against measles and mumps.
Topics: Cricetinae; Animals; Humans; Mice; SARS-CoV-2; COVID-19 Vaccines; Mumps; COVID-19; Measles-Mumps-Rubella Vaccine; Antibodies, Viral; Broadly Neutralizing Antibodies; Immunoglobulin G; Measles; Mesocricetus; Antibodies, Neutralizing; Spike Glycoprotein, Coronavirus
PubMed: 37796985
DOI: 10.1073/pnas.2220403120 -
Environmental Health Perspectives Dec 2023Prenatal exposures to certain poly- and perfluoroalkyl substances (PFAS) are associated with reduced humoral responses to some childhood immunizations.
Prenatal Exposure to Poly- and Perfluoroalkyl Substances (2009-2014) and Vaccine Antibody Titers of Measles, Mumps, Rubella, and Varicella in Children Four to Eight Years Old from the Healthy Start Cohort.
BACKGROUND
Prenatal exposures to certain poly- and perfluoroalkyl substances (PFAS) are associated with reduced humoral responses to some childhood immunizations.
OBJECTIVE
We estimated associations between prenatal PFAS exposure and child antibody titers for measles, mumps, rubella (MMR), and varicella after immunization.
METHODS
We measured serum antibody titers of 145 children (4-8 y old) enrolled in the Healthy Start cohort in Colorado, whose mothers had PFAS quantified mid-pregnancy (2009-2014). We used linear and logistic regression models to assess the relationship between five PFAS detected in of mothers and continuous or non-high-censored ("low") antibody titers and quantile g-computation to evaluate the overall effect of the PFAS mixture.
RESULTS
Median concentrations of individual PFAS were at or below the median reported among females in the United States. After receiving two vaccine doses, seropositive levels of antibodies were detected among most (93%-100%) children. Each log-unit increase in perfluorononanoate was associated with 2.09 [95% confidence interval (CI): 1.13, 3.87] times higher odds of a low measles titer, and each log-unit increase in perfluorooctanoate was associated with 2.46 (95% CI: 1.28, 4.75) times higher odds of a low mumps titer. Odds ratios for all other PFAS were elevated, but CIs included the null. Each quartile increase in the PFAS mixture was associated with 1.35 (95% CI: 0.80, 2.26) times higher odds of a low measles titer and 1.44 (95% CI: 0.78, 2.64) times higher odds of a low mumps titer. No significant associations were observed between PFAS and varicella or rubella antibodies. In stratified analyses, associations were negative among female children, except for perfluorohexane sulfonate and varicella, whereas they were positive among males.
DISCUSSION
Some prenatal PFAS were associated with lower antibody titers among fully immunized children. The potential for immunotoxic effects of PFAS requires further investigation in a larger study, because exposure is ubiquitous globally. https://doi.org/10.1289/EHP12863.
Topics: Child; Male; Pregnancy; Female; Humans; Child, Preschool; Chickenpox; Mumps; Prenatal Exposure Delayed Effects; Rubella; Measles; Vaccines; Fluorocarbons
PubMed: 38147368
DOI: 10.1289/EHP12863 -
Risk Analysis : An Official Publication... Sep 2023Vaccines can be seen as one of the greatest successes in modern medicine. Good examples are the vaccines against smallpox, polio, and measles. Unfortunately, vaccines...
Vaccines can be seen as one of the greatest successes in modern medicine. Good examples are the vaccines against smallpox, polio, and measles. Unfortunately, vaccines can have side effects, but the risks are considered by the health authorities and experts to be small compared to their benefits. Nevertheless, there are many who are skeptical of vaccination, something which has been very clearly demonstrated in relation to the COVID-19 disease. Risk is the key concept when evaluating a vaccine, in relation to both its ability to protect against the disease and its side effects. However, risk is a challenging concept to measure, which makes communication about vaccines' performance and side effects difficult. The present article aims at providing new insights into vaccine risks-the understanding, perception, communication, and handling of them-by adopting what is here referred to as a contemporary risk science perspective. This perspective clarifies the relationships between the risk concept and terms like uncertainty, knowledge, and probability. The skepticism toward vaccines is multifaceted, and influenced by concerns that extend beyond the effectiveness and safety of the vaccines. However, by clarifying the relationships between key concepts of risk, particularly how uncertainty affects risk and its characterization, we can improve our understanding of this issue.
PubMed: 37748932
DOI: 10.1111/risa.14228 -
PLOS Global Public Health 2023To better understand the declining rates of routine childhood vaccination in Brazil, we investigated the association between measles, mumps, and rubella (MMR) first dose...
To better understand the declining rates of routine childhood vaccination in Brazil, we investigated the association between measles, mumps, and rubella (MMR) first dose vaccine coverage and deprivation at the municipality level. Using routinely collected data from 5565 Brazilian municipalities from 2006 to 2020, we investigated the association between municipality-level MMR vaccine first dose coverage (i.e., as a continuous variable and as a percentage of municipalities attaining the 95% target coverage) in relation to quintiles of municipality-level deprivation, measured by the Brazilian Deprivation Index (Índice Brasileiro de Privação, IBP), and geographic regions. From 2006 to 2020, the mean municipality-level MMR vaccine coverage declined across all deprivation quintiles and regions of Brazil, by an average of 1.2% per year. The most deprived quintile of municipalities had higher coverage on average, but also the steepest declines in coverage (i.e., an annual decline of 1.64% versus 0.61% in the least deprived quintile) in the period of 2006-2020, and the largest drop in coverage at the beginning of the COVID-19 pandemic (2019-2020). Across all deprivation quintiles and regions (except for the Southeast region), less than 50% of municipalities in Brazil met the 95% MMR coverage target in 2020.The decrease in MMR first dose vaccine coverage in Brazil is widespread, but steeper declines have been observed in the most deprived municipalities. To promote vaccine equity and prevent future outbreaks, further research is urgently needed to understand the causal mechanisms underlying the observed associations between municipality-level MMR vaccine coverage and deprivation.
PubMed: 37527234
DOI: 10.1371/journal.pgph.0002027 -
The Lancet. Infectious Diseases Nov 2023After the devastating earthquake in Türkiye and Syria in February, 2023, the long-term failure to meet the need for shelter, unfavourable living conditions in tent... (Review)
Review
After the devastating earthquake in Türkiye and Syria in February, 2023, the long-term failure to meet the need for shelter, unfavourable living conditions in tent settlements, poor access to clean drinking water, water suitable for personal hygiene, and sanitary facilities, as well as interruptions in provision of primary health-care services, have emerged as the most important risk factors contributing to the spread of infectious diseases. 3 months after the earthquake, most of these problems persist in Türkiye. Data on the control of infectious diseases are scarce according to the reports prepared by medical specialist associations based on observations of health-care providers working in the region and statements made by the local health authorities. According to these unsystematised data, and considering the conditions in the region, faecal-oral transmissible gastrointestinal infections, as well as respiratory and vector-borne infections, are the main challenges. Vaccine-preventable diseases, such as measles, varicella, meningitis, and polio can be spread in temporary shelters due to interrupted vaccine services and crowded living conditions. In addition to controlling risk factors for infectious diseases, sharing data on the status and control of infectious diseases in the region with the community, health-care providers, and relevant expert groups should be a priority to improve the understanding of the effects of interventions and prepare for possible infectious disease outbreaks.
Topics: Humans; Earthquakes; Communicable Diseases; Disease Outbreaks; Health Services; Syria
PubMed: 37419128
DOI: 10.1016/S1473-3099(23)00362-6 -
Vaccines Nov 2023Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier-to-use, and more cost-effective means for the administration of vaccines than...
Safety, Tolerability, and Immunogenicity of Measles and Rubella Vaccine Delivered with a High-Density Microarray Patch: Results from a Randomized, Partially Double-Blinded, Placebo-Controlled Phase I Clinical Trial.
Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier-to-use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blinded, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18-50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3100 median cell-culture infectious dose [CCID] measles, ~4300 CCID rubella); high-dose MR-HD-MAPs (~9300 CCID measles, ~12,900 CCID rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1000 CCID per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2-8 °C for at least 24 months. When MR HD-MAPs stored at 2-8 °C for 24 months were transferred to 40 °C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates on day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7%, respectively, for measles, and 37.5%, 25.0% and 35.7%, respectively, for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.
PubMed: 38006057
DOI: 10.3390/vaccines11111725 -
Vaccines May 2024Measles seroprevalence data have potential to be a useful tool for understanding transmission dynamics and for decision making efforts to strengthen immunization... (Review)
Review
BACKGROUND
Measles seroprevalence data have potential to be a useful tool for understanding transmission dynamics and for decision making efforts to strengthen immunization programs. In this study, we conducted a systematized review and bias assessment of all primary data on measles seroprevalence in low- and middle-income countries (as defined by World Bank 2021 income classifications) published from 1962 to 2021.
METHODS
On 9 March 2022, we searched PubMed for all available data. We included studies containing primary data on measles seroprevalence and excluded studies if they were clinical trials or brief reports, from only health-care workers, suspected measles cases, or only vaccinated persons. We extracted all available information on measles seroprevalence, study design, and seroassay protocol. We conducted a bias assessment based on multiple categories and classified each study as having low, moderate, severe, or critical bias. This review was registered with PROSPERO (CRD42022326075).
RESULTS
We identified 221 relevant studies across all World Health Organization regions, decades, and unique age ranges. The overall crude mean seroprevalence across all studies was 78.0% (SD: 19.3%), and the median seroprevalence was 84.0% (IQR: 72.8-91.7%). We classified 80 (36.2%) studies as having severe or critical overall bias. Studies from country-years with lower measles vaccine coverage or higher measles incidence had higher overall bias.
CONCLUSIONS
While many studies have substantial underlying bias, many studies still provide some insights or data that could be used to inform modelling efforts to examine measles dynamics and programmatic decisions to reduce measles susceptibility.
PubMed: 38932314
DOI: 10.3390/vaccines12060585 -
The Lancet. Infectious Diseases Jan 2024
Topics: Humans; Rubella; Vaccination; Measles; Disease Outbreaks; Measles-Mumps-Rubella Vaccine
PubMed: 38141646
DOI: 10.1016/S1473-3099(23)00771-5 -
International Journal of Infectious... Dec 2023During the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and safety of concomitant administration of the sabin-strain-based inactivated poliovirus vaccine, the diphtheria-tetanus-acellular pertussis vaccine, and measles-mumps-rubella vaccine to healthy infants aged 18 months in China.
OBJECTIVES
During the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential solutions to alleviate this predicament. Our objective is to delve into the concurrent administration of the sabin-strain-based inactivated poliovirus vaccine (sIPV), the diphtheria-tetanus-acellular pertussis vaccine (DTaP), and measles-mumps-rubella vaccine (MMR), with the intention of bridging the evidentiary gap pertaining to vaccine co-administration in Chinese infants, and to ensure a safe and effective vaccination strategy, ultimately leading to an augmentation in immunization coverage.
METHODS
This study was a follow-up trial of the "Immunogenicity and safety of concomitant administration of the sIPV with the DTaP vaccine in children: a multicenter, randomized, non-inferiority, controlled trial." Blood samples were collected on day 0 and day 30, and serum antibody levels were detected to measure antibody responses to each of the antigens. Local and systemic adverse events were monitored and compared among groups. This study is the first to fill the knowledge gap in China regarding the safe and effective combined vaccination of sIPV, DTaP, and MMR vaccines.
RESULTS
The geometric mean titer of the poliovirus types I, II, and III neutralizing antibodies were 1060.22 (95% CI: 865.73-1298.39), 1537.06 (95% CI: 1324.27-1784.05), and 1539.10 (95% CI: 1296.37-1827.29) in group I on day 30; geometric mean titer of antibodies against DTaP and MMR in the simultaneous vaccination group was non-inferior to those in the DTaP alone and MMR alone group. Reporting rates of local and systemic adverse reactions were similar between groups and no serious adverse events were reported throughout the clinical study period.
CONCLUSION
Co-administration of the sIPV, DTaP, and MMR was safe and did not impact immunogenicity, which would help to mitigate administrative costs and enhance vaccine coverage rates.
Topics: Child; Humans; Infant; Diphtheria-Tetanus-acellular Pertussis Vaccines; Measles-Mumps-Rubella Vaccine; Poliovirus Vaccine, Inactivated; Pandemics; Vaccines, Combined; Poliovirus; Diphtheria-Tetanus-Pertussis Vaccine; Haemophilus Vaccines; Antibodies, Bacterial; Immunization Schedule
PubMed: 37832931
DOI: 10.1016/j.ijid.2023.10.006 -
Vaccines Jun 2024No vaccine has been more effective in reducing disease burden, especially in preventing child deaths, than measles-containing vaccine. The return on investment makes...
No vaccine has been more effective in reducing disease burden, especially in preventing child deaths, than measles-containing vaccine. The return on investment makes measles-containing vaccine one of the most cost-effective public health measures available. Exhaustive reviews of biological, technical, economic and programmatic evidence have concluded that measles can and should be eradicated, and by including rubella antigen in measles-containing vaccine, congenital rubella syndrome will also be eradicated. All World Health Organisation Regions have pledged to achieve measles elimination. Unfortunately, not all countries and global partners have demonstrated an appropriate commitment to these laudable public health goals, and the negative impact of the COVID-19 pandemic on coverage rates has been profound. Unsurprisingly, large disruptive outbreaks are already occurring in many countries with a global epidemic curve ominously similar to that of 2018/2019 emerging. The Immunization Agenda 2030 will fail dismally unless measles and rubella eradication efforts are accelerated. Over half of all member states have been verified to have eliminated rubella and endemic rubella transmission has not been re-established in any country to date. In 2023, 84 countries and areas were verified to have sustained elimination of measles. However, without a global target, this success will be difficult to sustain. Now is the time for a global eradication goal and commitment by the World Health Assembly. Having a galvanising goal, with a shared call for action, will demand adequate resourcing from every country government and global partners. Greater coordination across countries and regions will be necessary. Measles, rubella and congenital rubella syndrome eradication should not remain just a technically feasible possibility but rather be completed to ensure that future generations of children do not live under the shadow of preventable childhood death and lifelong disability.
PubMed: 38932428
DOI: 10.3390/vaccines12060699