Vaccine Shortage Research Articles

Hierarchical Vaccine Allocation Based on Epidemiological and Behavioral Considerations.

Vaccines have proven useful in curbing contagion from new strains of the SARS-CoV-2 virus. However, equitable vaccine allocation continues to be a significant challenge worldwide, necessitating a comprehensive allocation strategy incorporating heterogeneity in epidemiological and behavioral considerations. In this paper, we present a hierarchical allocation strategy that assigns vaccines to zones and their constituent neighborhoods cost-effectively, based on their population density, susceptibility, infected count, and attitude towards vaccinations. Moreover, it includes a module that tackles vaccine shortages in certain zones by locally transferring vaccines from zones with surplus vaccines. We leverage the epidemiological, socio-demographic, and social media datasets from Chicago and Greece and their constituent community areas to show that the proposed allocation approach assigns vaccines based on the chosen criteria and captures the effects of disparate vaccine adoption rates. We conclude the paper with a lowdown on future efforts to extend this study to design models for effective public policies and vaccination strategies that curtail vaccine purchase costs.

People’s perceptions on COVID-19 vaccination: an analysis of twitter discourse from four countries

More than six and half million people have died as a result of the COVID-19 pandemic till Dec 2022. Vaccination is the most effective means to prevent mortality and infection attributed to COVID-19. Identifying public attitudes and perceptions on COVID-19 vaccination is essential to strengthening the vaccination programmes. This study aims to identify attitudes and perceptions of twitter users towards COVID-19 vaccinations in four different countries. A sentiment analysis of 663,377 tweets from October 2020 to September 2022 from four different countries (i.e., India, South Africa, UK, and Australia) was conducted. Text mining using roBERTA (Robustly Optimized Bert Pretraining approach) python library was used to identify the polarity of people’s attitude as "negative", "positive" or "neutral" based on tweets. A sample of 2000 tweets (500 from each country) were thematically analysed to explore the people’s perception concerning COVID-19 vaccines across the countries. The attitudes towards COVID-19 vaccines varied by countries. Negative attitudes were observed to be highest in India (58.48%), followed by United Kingdom (33.22%), Australia (31.42%) and South Africa (28.88%). Positive attitudes towards vaccines were highest in the United Kingdom (21.09%). The qualitative analysis yielded eight themes namely (i) vaccine shortages, (ii) vaccine side-effects, (iii) distrust on COVID-19 vaccines, (iv) voices for vaccine equity, (v) awareness about vaccines, (vi) myth busters, (vii) vaccines work and (viii) vaccines are safe. The twitter discourse reflected the evolving situation of COVID-19 pandemic and vaccination strategies, lacunae and positives in the respective countries studied.

Evaluation of vaccine rollout strategies for emerging infectious diseases: A model-based approach including protection attitudes

Vaccine allocation strategies become crucial during vaccine shortages, especially in the face of potential outbreaks of new infectious diseases, as witnessed during the COVID-19 pandemic. To address this, a specialized compartmental model is created, which simulates an emerging infectious disease similar to COVID-19. This model divides the population into different age groups and is used to compare various vaccine prioritisation approaches, aiming to minimize the total number of fatalities. The model is an improvement upon previous ones as it incorporates essential behavioural factors and is adapted to account for the protective effects of vaccination against both disease infection and transmission. It takes into account human behaviors such as mask-wearing and social distancing by utilizing specific parameters related to self-protection, awareness levels, and the frequency of daily person-to-person interactions within each age group. Furthermore, a novel method for dynamic vaccine prioritisation was introduced in this study. This approach is model-independent and relies on the dynamic R number. It is the first time such a method has been developed, offering a decision-making approach that is not tied to any specific model. This innovation provides a flexible and adaptable strategy for determining vaccine priorities based on real-time data and the current state of the outbreak.Our findings reveal crucial insights into vaccine allocation strategies. When the daily rollout rates are fast (0.75% or higher) and children are eligible for vaccination, prioritising groups with high daily person-to-person interactions can lead to substantial reductions in total fatalities (up to approximately 40% lower). On the other hand, if rollout rates are slower and overall vaccination coverage is high, focusing on vaccinating elders emerges as the most effective strategy, resulting in up to approximately 10% fewer fatalities. However, the scenario changes significantly when children are not eligible for vaccination, as they constitute a highly interactive population group. In this case, the differences between priority strategies become smaller. With fast daily rollout rates, prioritisation based on interactions achieves only a 7% reduction in total fatalities, while a slower rollout with vaccination of elders first leads to an approximately 11% reduction in fatalities compared to the scenario where children are eligible for vaccination. The impact of behavioural parameters is equally critical. When the self-protection levels exercised by the population are low, it significantly affects the optimal vaccine prioritisation strategy to be followed, making it essential to consider behavioural factors in decision-making.

Monitoring the COVID-19 Vaccine Acceptance Trend and its Determinants Among Iranian Adults.

Vaccination seems to be the most critical means of halting the COVID-19 pandemic. It is crucial to understand the factors that influence COVID-19 vaccine acceptance to avoid low vaccination rates. This study intended to monitor the COVID-19 vaccine acceptance and its association with socio-demographic factors and prior diagnosis of COVID-19 in Iranian adults during the COVID-19 pandemic. The study utilized data from the COVID-19 Population Survey of Iran (COPSIR), a repeated national survey designed to monitor COVID-19-related behavioral insights. From April 2020 to November 2021, thirteen iterations of a series of cross-sectional studies involving computer-assisted telephone interviews were conducted. The COVID-19 vaccine acceptance rate remained above 80% until the ninth wave in February 2021, when it dropped to 62.9%. However, throughout the next four surveys, it rose gradually from 72.0% to 85.7%. The multilevel regression model revealed that the COVID-19 vaccine acceptance was significantly and positively linked with age and education. Despite the relatively high COVID-19 vaccine acceptance rate among Iranian adults, after the emergence of vaccines on the global market and controversies about their safety in Iran, the initially high vaccine acceptance rate dropped significantly, and then increased over time and returned to its peak level (85%). According to the Commodity Theory, this rise in vaccine acceptance can be attributed to the COVID-19 vaccine shortage in the country between January and July 2022. For Iranian adults to accept vaccines more readily, health promotion programs should target the youth and the less literate adults.

Risk assessment and antibody responses to SARS-CoV-2 in healthcare workers.

Preventing infection in healthcare workers (HCWs) is crucial for protecting healthcare systems during the COVID-19 pandemic. Here, we investigated the seroepidemiology of SARS-CoV-2 in HCWs in Norway with low-transmission settings. From March 2020, we recruited HCWs at four medical centres. We determined infection by SARS-CoV-2 RT-PCR and serological testing and evaluated the association between infection and exposure variables, comparing our findings with global data in a meta-analysis. Anti-spike IgG antibodies were measured after infection and/or vaccination in a longitudinal cohort until June 2021. We identified a prevalence of 10.5% (95% confidence interval, CI: 8.8-12.3) in 2020 and an incidence rate of 15.0 cases per 100 person-years (95% CI: 12.5-17.8) among 1,214 HCWs with 848 person-years of follow-up time. Following infection, HCWs (n = 63) mounted durable anti-spike IgG antibodies with a half-life of 4.3 months since their seropositivity. HCWs infected with SARS-CoV-2 in 2020 (n = 46) had higher anti-spike IgG titres than naive HCWs (n = 186) throughout the 5 months after vaccination with BNT162b2 and/or ChAdOx1-S COVID-19 vaccines in 2021. In a meta-analysis including 20 studies, the odds ratio (OR) for SARS-CoV-2 seropositivity was significantly higher with household contact (OR 12.6; 95% CI: 4.5-35.1) and occupational exposure (OR 2.2; 95% CI: 1.4-3.2). We found high and modest risks of SARS-CoV-2 infection with household and occupational exposure, respectively, in HCWs, suggesting the need to strengthen infection prevention strategies within households and medical centres. Infection generated long-lasting antibodies in most HCWs; therefore, we support delaying COVID-19 vaccination in primed HCWs, prioritising the non-infected high-risk HCWs amid vaccine shortage.

Perencanaan Kebijakan Persediaan Vaksin Booster Dengan Metode Continuous Review (s,S) Untuk Mengurangi Overstock Di Rumah Sakit Tentara Kota Pematangsiantar

Pematangsiantar City Army Hospital is one of the state-owned health facilities that provides booster vaccination services with 4 types of booster vaccines available, namely sinovac, astrazeneca, pfizer and moderna. The uncertain level of demand for booster vaccines causes the Pematangsiantar City Army Hospital to require booster vaccine inventory policy planning using the continuous review (s,S) method to prevent overstock which results in considerable cost expenditures. From the calculation of booster vaccine inventory control using the continuous review method (s,S), it is obtained that the total inventory cost has a significant percentage change. For the type of sinovac, the percentage change in total inventory costs reaches 92% of the total inventory costs in the existing conditions, for astrazeneca reaches 58% of the total inventory costs in the existing conditions, for pfizer reaches 60% of the total inventory costs in the existing conditions, and for moderna reaches 95% of the total inventory costs in the existing conditions. The results of the calculation of the total cost of inventory with continuous review (s,S) can provide a decrease in costs incurred by the Pematangsiantar City Army Hospital. This is because the continuous review (s,S) inventory policy minimises the cost of vaccine shortages which are quite costly.

Jumping the Queue:Willingness to Pay for Faster Access to COVID-19 Vaccines in Seven European Countries.

Given the initial shortage of vaccines to protect against coronavirus disease 2019 (COVID-19), many countries set up priority lists, implying that large parts of the population had to wait. We therefore elicited the willingness to pay (WTP) for access to two hypothetical COVID-19 vaccines. Respondents were asked how much they would be willing to pay to get an immediate COVID-19 vaccination rather than waiting for one through the public system. We report data collected in January/February 2021 from the European COVID Survey (ECOS) comprising representative samples of the population in Denmark, France, Germany, Italy, Portugal, the Netherlands, and the UK (N=7068). In total, 73% (68.5%) of respondents were willing to pay for immediate access to a 100% (60%) effective vaccine, ranging from 66.4% (59.4%) in the Netherlands to 83.3% (81.1%) in Portugal. We found a mean WTP of 54.36 euros (median 37 euros) for immediate access to the 100% effective COVID-19 vaccine and 43.83 euros (median 31 euros) for the 60% effective vaccine. The vaccines' effectiveness, respondents' age, country of residence, income, health state and well-being were significant determinants of WTP. Willingness to be vaccinated (WTV) was also strongly associated with WTP, with lower WTV being associated with lower WTP. A higher perceived risk of infection, higher health risk, more trust in the safety of vaccines, and higher expected waiting time for the free vaccination were all associated with a higher WTP. We find that most respondents would have been willing to pay for faster access to COVID vaccines (jumping the queue), suggesting welfare gains from quicker access to these vaccines. This is an important result in light of potential future outbreaks and vaccines.

Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.

All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.

An impact assessment of the use of aerial logistics to improve access to vaccines in the Western-North Region of Ghana

BackgroundPrevention of infectious diseases among children is crucial to improve child health and survival. However, many countries in Sub-Saharan Africa struggle to achieve vaccination targets due to supply chain challenges, which lead to vaccine shortages, stockouts, and increased costs. We evaluated the effects of aerial logistics (centralized storage and delivery by drones) on vaccine stock, stockouts, vaccination coverage and vaccine preventable outcomes in the Western North Region of Ghana. MethodsThe study combined retrospective quasi-experimental and cross-sectional designs to evaluate supply chain, programmatic, and clinical outcomes. Surveys to health providers were used to collect information from a random sample of 156 facilities, and secondary data on vaccination coverage and clinical outcomes was analyzed at the district level for the years 2017–2021. ResultsFacilities served by aerial logistics reported significant reductions in the duration of vaccine stockouts (30 %, p-value < 0.05), as well as in the frequency of missed opportunities for vaccination (44 %, p-value < 0.05). Being served by aerial logistics was associated with increased satisfaction with access to vaccines. Significant differences in vaccination coverage were found for most vaccines, in a range between 13.1 and 37.5 percentage points in vaccination coverage for served districts. Infectious diarrhea cases in children between 5 and 9 years old were reduced by 41.6 % (p-value < 0.05). ConclusionEnd-to-end aerial logistics appears as an effective tool to improve the performance of the supply chain for vaccines. The strategy potentially increases the resilience of the health system and contributes to increased vaccination coverage and higher levels of satisfaction among providers in the Western North Region of Ghana.

Common Adverse Events from Mixing COVID-19 Vaccine Booster in Hanoi, Vietnam.

Mixing vaccines was proposed as a solution to tackle supply chain interruptions during the crisis of the COVID-19 pandemic. This study aimed to investigate the safety of mixing COVID-19 vaccines for a booster dose in Hanoi, Vietnam. A cross-sectional study was conducted via a telephone-based interview to identify the adverse events following COVID-19 vaccination among 719 participants in Hanoi, Vietnam. In total, 45.76% of participants experienced at least one adverse event following two doses of the COVID-19 vaccine. Most of the adverse events were local effects with mild symptoms such as fever, headache, muscle pain, and/or pain at the site. In general, matching two doses in the same vaccines was not associated with the adverse events as compared to mixing vaccines (OR = 1.43, 96%CI: 0.93-2.2), except matching two doses of Pfizer (OR = 2.25, 95%CI: 1.33-3.82). The findings of this study suggest the overall safety of mixed vaccination. In light of the vaccine shortage, mixing vaccinations for COVID-19 prevention is a good solution. Further studies with larger cohorts and investigating immunity following mixing vaccines are needed to elucidate the mechanism.

Genomic Surveillance of SARS-CoV-2 Variants That Emerged in South and Southeast Asia during Early 2022.

The continuously emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have made the global coronavirus disease 2019 (COVID-19) pandemic unpredictable. Since the beginning of the pandemic, densely populated South and Southeast Asia have suffered great losses due to multiple COVID-19 surges because of vaccine and other medical resource shortages. Therefore, it is crucial to closely monitor the SARS-CoV-2 epidemic and to understand the evolutionary and transmission characteristics of SARS-CoV-2 in these regions. Here, we document the evolution of epidemic strains in the Philippines, Pakistan, and Malaysia from late 2021 to early 2022. Our results confirmed the circulation of at least five SARS-CoV-2 genotypes in these countries in January 2022, when Omicron BA.2, with a detection rate of 69.11%, replaced Delta B.1.617 as the dominant strain. Single-nucleotide polymorphism analysis indicated the distinct evolutionary directions of the Omicron and Delta isolates, with S, Nsp1, and Nsp6 genes potentially playing a significant role in the host adaptation of the Omicron strain. These findings are able to provide insights for predicting the evolutionary direction of SARS-CoV-2 in terms of variant competition, developing multi-part vaccines, and to support the evaluation and adjustment of current surveillance, prevention, and control strategies in South and Southeast Asia.

A systematic review of nudges on hand hygiene against the spread of COVID-19

The COVID-19 pandemic has posed the greatest threat to global health over the last three years. Due to the temporary shortage of appropriate vaccines, a systematic change in human behaviour is necessary to keep the spread of the virus under control, increasing the quality of basic hygiene practices, such as systematic hand hygiene. Nudges are increasingly used in public health interventions to promote critical preventive hygiene behaviours. This review aimed to investigate the effect and the characteristics of nudges on hand hygiene, as a COVID-19 preventive measure. We systematically reviewed the relevant literature from January 2008 to November 2020. A total of 15 articles met the inclusion criteria. The findings of this review showed that most of the nudging interventions had a positive effect on hand hygiene. Nudges should be included in the existing and future public health interventions to prevent the spread of COVID-19 and future pandemics, rather than being an alternative and unconventional tool for public health policies.

COVID-19 Vaccine Rollout Plans Should Consider Spatial Distribution of Age-Specific Population

In the early phases of COVID-19 vaccine distribution, most countries adopted age-based rollout plans due to vaccine shortages. The plans, however, might overlook different spatial distributions of each age group. In this study, we first examine separate spatial accessibility to vaccine sites varying by different age groups, transportation modes, and times to find differences in spatial patterns of accessibility scores based on the enhanced two-step floating catchment area method. We also investigate spatial inequality in measured accessibility through the Gini coefficient. Finally, we scrutinize to what extent spatial accessibility to vaccine sites is overestimated or underestimated by different age groups. Results showed that there is spatial disparity in accessibility scores between the total population and multiple age-stratified groups. We also found that transportation modes play a significant role in determining spatial patterns of accessibility to vaccine locations, whereas time was not a major factor making differences in spatial accessibility patterns. Our findings suggest that vaccine rollout plans should incorporate age-specific population distribution to maximize accessibility and minimize spatial disparity.

Immunogenicity and reactogenicity of mRNA COVID-19 vaccine booster administered by intradermal or intramuscular route in Thai Older adults.

Intradermal (ID) vaccination may alleviate COVID-19 vaccine shortages and vaccine hesitancy. Persons aged ≥65 years who were vaccinated with 2-dose ChAdOx1 12-24 weeks earlier were randomized to receive a booster vaccination by either ID (20-mcg mRNA1273 or 10-mcg BNT162b2) or intramuscular (IM) (100-mcg mRNA1273 or 30-mcg BNT162b2) route. Anti-receptor binding domain (anti-RBD) IgG, neutralizing antibody (NAb), and IFNγ-producing cells were measured at 2-4 weeks following vaccination. Of 210 participants enrolled, 70.5% were female and median age was 77.5 years (interquartile range: 71-84). Following booster dose, both ID vaccination induced 37% lower levels of anti-RBD IgG than IM vaccination of the same vaccine. NAb titers against ancestral and omicron BA.1 was highest following IM mRNA-1273 (geometric mean 1,718 and 617), followed by ID mRNA-1273 (1,212 and 318), IM BNT162b2 (713 and 230), and ID BNT162b2 (587 and 148), respectively. Spike-specific IFNγ responses were similar or higher in the ID groups when compared with IM groups. ID route tended to have lower systemic AEs, although more local AEs reported in ID mRNA-1273 group. Fractional ID vaccination induced lower humoral but comparable cellular immunity compared to IM and may be an alternative option for older people.

Immunogenicity and safety of fractional doses of 17D-213 yellow fever vaccine in children (YEFE): a randomised, double-blind, non-inferiority substudy of a phase 4 trial

Current supply shortages constrain yellow fever vaccination activities, particularly outbreak response. Although fractional doses of all WHO-prequalified yellow fever vaccines have been shown to be safe and immunogenic in a randomised controlled trial in adults, they have not been evaluated in a randomised controlled trial in young children (9-59 months old). We aimed to assess the immunogenicity and safety of fractional doses compared with standard doses of the WHO-prequalified 17D-213 vaccine in young children. This substudy of the YEFE phase 4 study was conducted at the Epicentre Mbarara Research Centre (Mbarara, Uganda). Eligible children were aged 9-59 months without contraindications for vaccination, without history of previous yellow fever vaccination or infection and not requiring yellow fever vaccination for travelling. Participants were randomly assigned, using block randomisation, 1:1 to standard or fractional (one-fifth) dose of yellow fever vaccine. Investigators, participants, and laboratory personnel were blinded to group allocation. Participants were followed for immunogenicity and safety at 10 days, 28 days, and 1 year after vaccination. The primary outcome was non-inferiority in seroconversion (-10 percentage point margin) 28 days after vaccination measured by 50% plaque reduction neutralisation test (PRNT50) in the per-protocol population. Safety and seroconversion at 10 days and 12-16 months after vaccination (given COVID-19 resctrictions) were secondary outcomes. This study is registered with ClinicalTrials.gov, NCT02991495. Between Feb 20, 2019, and Sept 9, 2019, 433 children were assessed, and 420 were randomly assigned to fractional dose (n=210) and to standard dose (n=210) 17D-213 vaccination. 28 days after vaccination, 202 (97%, 95% CI 95-99) of 207 participants in the fractional dose group and 191 (100%, 98-100) of 191 in the standard dose group seroconverted. The absolute difference in seroconversion between the study groups in the per-protocol population was -2 percentage points (95% CI -5 to 1). 154 (73%) of 210 participants in the fractional dose group and 168 (80%) of 210 in the standard dose group reported at least one adverse event 28 days after vaccination. At 10 days follow-up, seroconversion was lower in the fractional dose group than in the standard dose group. The most common adverse events were upper respiratory tract infections (n=221 [53%]), diarrhoea (n=68 [16%]), rhinorrhoea (n=49 [12%]), and conjunctivitis (n=28 [7%]). No difference was observed in incidence of adverse events and serious adverse events between study groups. Fractional doses of the 17D-213 vaccine were non-inferior to standard doses in inducing seroconversion 28 days after vaccination in children aged 9-59 months when assessed with PRNT50, but we found fewer children seroconverted at 10 days. The results support consideration of the use of fractional dose of yellow fever vaccines in WHO recommendations for outbreak response in the event of a yellow fever vaccine shortage to include children. Médecins Sans Frontières Foundation.

Summary of the National Advisory Committee on Immunization (NACI) Statement-Recommendations on Fractional Influenza Vaccine Dosing in the Event of a Shortage: Pandemic preparedness.

At the commencement of a pandemic, it is important to consider the impact of respiratory infections on the health system and the possibility of vaccine shortages due to increased demand. In the event of an influenza vaccine shortage, a strategy for administration of fractional influenza vaccine doses might be considered. This article reviews the available evidence for efficacy, effectiveness, immunogenicity and safety of fractional influenza vaccine dosing, and summarizes the National Advisory Committee on Immunization (NACI) recommendations on fractional dosing strategies by public health programs in Canada. Two rapid literature reviews were undertaken to evaluate the efficacy, effectiveness, immunogenicity and safety of fractional influenza vaccine dosing via the intramuscular or intradermal route. The NACI evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and apply an ethics, equity, feasibility and acceptability lens to develop recommendations. There was limited evidence for the effectiveness of fractional influenza vaccine dosing. Fractional dosing studies were primarily conducted in healthy individuals, mainly young children and infants, with no underlying chronic conditions. There was fair evidence for immunogenicity and safety. Feasibility issues were identified with intradermal use in particular. NACI recommended that, in the event of a significant population-level shortage of influenza vaccine, a full-dose influenza vaccine should continue to be used, and existing vaccine supply should be prioritized for those considered to be at high risk or capable of transmitting to those at high risk of influenza-related complications or hospitalizations. NACI recommended against the use of fractional doses of influenza vaccine in any population.

Human Papillomavirus vaccines: Call for a European change to tackle current and future shortages

ContextThere is a global Human Papillomavirus (HPV) vaccine shortage until 2024. The World Health Organization recommended a temporary suspension of HPV vaccination for boys until all girls who need the vaccine can get it. In the European Union (EU), practices to define and monitor HPV vaccine shortages differ between the Member States. Prior policy initiatives were insufficient to address current vaccine shortages.Policy optionsDifferent policy options are recommended, divided into three self-developed clusters: prevention, response, and supply side. The policy options for the prevention part include decentralised surveillance and centralised surveillance. The policy options for the response part include dose sparing, EU joint procurement, postponing injection for young children, postponing vaccination for boys, and prioritisation in favour of low- and middle-income countries. The policy option for the supply side part is novel procurement agreements.RecommendationsA traffic light system to assist policymakers has been developed. The traffic light system recommends when policymakers should implement the suggested policy options. The traffic light system describes four stages: Green light (shortage prevention); Amber light (imminent shortage prevention); Red light (shortage management); Shortage lessons. These recommendations will improve EU crisis management.

Enhanced safety surveillance of STAMARIL® yellow fever vaccine provided under the expanded access investigational new drug program in the USA.

YF-VAX® (Sanofi, Swiftwater, PA), a live, attenuated vaccine based on the yellow fever (YF) substrain 17D-204, is the only YF vaccine licensed in the USA. Manufacturing disruption of YF-VAX and anticipated depletion of the US supply by mid-2017 led to the importation of another YF vaccine, STAMARIL® (Sanofi, France), into the USA under an expanded access investigational new drug program (EAP) to fulfil the public health need for YF vaccination. As part of this program, Sanofi collected enhanced safety surveillance data following vaccination with STAMARIL. Here, we report the results of the enhanced safety surveillance. STAMARIL vaccine was offered to those aged ≥9months at high risk of YF. Vaccine recipients (or parents/guardians) were instructed to report suspected adverse reactions, any serious adverse events (SAEs) including adverse events of special interest [AESI] occurring after vaccination regardless of suspected relationship, and any inadvertent exposure in pregnancy or breastfeeding within 14days of vaccination. The AESIs monitored were anaphylaxis, neurotropic disease (YEL-AND) and viscerotropic disease (YEL-AVD). Overall, 627 079 individuals received STAMARIL from May 2017 through June 2021; of these, 1308 (0.2%) reported at least one AE, of which 122 reported at least one SAE. There were seven cases of YEL-AND and three cases of YEL-AVD reported, for reporting rates of 1.1 and 0.5 per 100 000 vaccine recipients, respectively. One vaccine recipient developed an anaphylactic reaction (reporting rate: 0.16 per 100 000). No safety concerns were identified from inadvertent vaccine exposure during pregnancy (41 pregnant women) or potential neonatal exposure via breast milk (four exposed infants). This study supports the utility of STAMARIL in the EAP as an alternative solution for the YF vaccine shortage in the USA. SAEs were very rare and consistent with the known safety profile of STAMARIL.

Evaluation of mpox vaccine dose-sparing strategies.

The spring-summer 2022 mpox outbreak had over 50,000 cases globally, most of them in gay, bisexual, and other men who have sex with men (MSM). In response to vaccine shortages, several countries implemented dose-sparing vaccination strategies, stretching a full-dose vaccine vial into up to five fractional-dose vaccines. Recent studies have found mixed results regarding the effectiveness of the mpox vaccine, raising the question of the utility of dose-sparing strategies. We used an age- and risk-stratified mathematical model of an urban MSM population in the United States with ∼12% high-risk MSM to evaluate potential benefits from implementing dose-sparing vaccination strategies in which a full dose is divided into 3.5 fractional doses. We found that results strongly depend on the fractional-dose vaccine effectiveness (VE) and vaccine supply. With very limited vaccines available, enough to protect with a full dose approximately one-third of the high-risk population, dose-sparing strategies are more beneficial provided that fractional doses preserved at least 40% of full-dose effectiveness (34% absolute VE), projecting 13% (34% VE) to 70% (68% absolute VE) fewer infections than full-dose strategies. In contrast, if vaccine supply is enough to cover the majority of the high-risk population, dose-sparing strategies can be outperformed by full-dose strategies. Scenarios in which fractional dosing was 34% efficacious resulted in almost three times more infections than full dosing. Our analysis suggests that when mpox vaccine supply is limited and fractional-dose vaccination retains moderate effectiveness, there are meaningful health benefits from providing a smaller dose to a larger number of people in the high-risk population. These findings should inform the public-health response to future mpox outbreaks.

Humoral and T Cell Immune Responses against SARS-CoV-2 after Primary and Homologous or Heterologous Booster Vaccinations and Breakthrough Infection: A Longitudinal Cohort Study in Malaysia.

Vaccine efficacy against SARS-CoV-2 could be compromised by the emergence of SARS-CoV-2 variants and it is important to study how it impacts the booster vaccination regime. We investigated the humoral and T cell responses longitudinally in vaccinated uninfected (n = 25) and post-COVID-19 individuals (n = 8), and those who had received a BNT162b2 booster following complete two-doses regimes of either BNT162b2 (homologous) (n = 14) or ChAdOx1-S (heterologous) (n = 15) vaccines, by means of a SARS-CoV-2 pseudovirus neutralization test and QuantiFERON SARS-CoV-2 assay. Vaccinated post-COVID-19 individuals showed higher neutralizing antibodies with longer durability against SARS-CoV-2 wild type (WT) and Omicron spikes, but demonstrated similar declining T cell responses compared to the uninfected vaccinated. Two doses of BNT162b2 induced higher neutralizing antibodies against WT and T cell responses than ChAdOx1-S for six months. The BNT162b2 booster confers a greater humoral response against WT, but a similar cross-neutralizing antibody against Omicron and T cell responses in the homologous booster group compared to the heterologous booster group. Breakthrough infection in the homologous booster group (n = 11) significantly increased the neutralizing antibody, but T cell responses remained low. Our data may impact government public health policy regarding the administration of mix-and-match vaccines, where both vaccination regimes can be employed should there be shortages of certain vaccines.