Covid19Vaxplorer: A free, online, user-friendly COVID-19 vaccine allocation comparison tool.

There are many COVID-19 vaccines currently available, however, Low- and middle-income countries (LMIC) still have large proportions of their populations unvaccinated. Decision-makers must decide how to effectively allocate available vaccines (e.g. boosters or primary series vaccination, which age groups to target) but LMIC often lack the resources to undergo quantitative analyses of vaccine allocation, resulting in ad-hoc policies. We developed Covid19Vaxplorer (https://covid19vaxplorer.fredhutch.org/), a free, user-friendly online tool that simulates region-specific COVID-19 epidemics in conjunction with vaccination with the purpose of providing public health officials worldwide with a tool for vaccine allocation planning and comparison. We developed an age-structured mathematical model of SARS-CoV-2 transmission and COVID-19 vaccination. The model considers vaccination with up to three different vaccine products, primary series and boosters. We simulated partial immunity derived from waning of natural infection and vaccination. The model is embedded in an online tool, Covid19Vaxplorer that was optimized for its ease of use. By prompting users to fill information through several windows to input local parameters (e.g. cumulative and current prevalence), epidemiological parameters (e.g basic reproduction number, current social distancing interventions), vaccine parameters (e.g. vaccine efficacy, duration of immunity) and vaccine allocation (both by age groups and by vaccination status). Covid19Vaxplorer connects the user to the mathematical model and simulates, in real time, region-specific epidemics. The tool then produces key outcomes including expected numbers of deaths, hospitalizations and cases, with the possibility of simulating several scenarios of vaccine allocation at once for a side-by-side comparison. We provide two usage examples of Covid19Vaxplorer for vaccine allocation in Haiti and Afghanistan, which had as of Spring 2023, 2% and 33% of their populations vaccinated, and show that for these particular examples, using available vaccine as primary series vaccinations prevents more deaths than using them as boosters.

Covid19Vaxplorer: a free, online, user-friendly COVID-19 Vaccine Allocation Comparison Tool.

Background: There are many COVID-19 vaccines currently available, however, Low- and middle-income countries (LMIC) still have large proportions of their populations unvaccinated. Decision-makers must decide how to effectively allocate available vaccines (e.g. boosters or primary series vaccination, which age groups to target) but LMIC often lack the resources to undergo quantitative analyses of vaccine allocation, resulting in ad-hoc policies. We developed Covid19Vaxplorer (https://covid19vaxplorer.fredhutch.org/), a free, user-friendly online tool that simulates region-specific COVID-19 epidemics in conjunction with vaccination with the purpose of providing public health officials worldwide with a tool for vaccine allocation planning and comparison. Methods: We developed an age-structured mathematical model of SARS-CoV-2 transmission and COVID-19 vaccination. The model considers vaccination with up to three different vaccine products, primary series and boosters. We simulated partial immunity derived from waning of natural infection and vaccination. The model is embedded in an online tool, Covid19Vaxplorer that was optimized for its ease of use. By prompting users to fill information through several windows to input local parameters (e.g. cumulative and current prevalence), epidemiological parameters (e.g basic reproduction number, current social distancing interventions), vaccine parameters (e.g. vaccine efficacy, duration of immunity) and vaccine allocation (both by age groups and by vaccination status). Covid19Vaxplorer connects the user to the mathematical model and simulates, in real time, region-specific epidemics. The tool then produces key outcomes including expected numbers of deaths, hospitalizations and cases, with the possibility of simulating several scenarios of vaccine allocation at once for a side-by-side comparison. Results: We provide two usage examples of Covid19Vaxplorer for vaccine allocation in Haiti and Afghanistan, which had as of Spring 2023 2% and 33% of their populations vaccinated, and show that for these particular examples, using available vaccine as primary series vaccinations prevents more deaths than using them as boosters. Covid19Vaxplorer allows users in 183 regions in the world to compare several vaccination strategies simultaneously, adjusting parameters to their local epidemics, infrastructure and logistics. Covid19Vaxplorer is an online, free, user-friendly tool that facilitates evidence-based decision making for vaccine distribution.

Retrospective analysis of equity-based optimization for COVID-19 vaccine allocation.

Marginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counterfactual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American-Indian or Alaska-Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.

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.

Retrospective Analysis of Equity-Based Optimization for COVID-19 Vaccine Allocation.

Marginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counter-factual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American Indian or Alaska Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.

Could widespread use of antiviral treatment curb the COVID-19 pandemic? A modeling study.

BACKGROUND: Despite the development of safe and effective vaccines, effective treatments for COVID-19 disease are still urgently needed. Several antiviral drugs have shown to be effective in reducing progression of COVID-19 disease. METHODS: In the present work, we use an agent-based mathematical model to assess the potential population impact of the use of antiviral treatments in four countries with different demographic structure and current levels of vaccination coverage: Kenya, Mexico, United States (US) and Belgium. We analyzed antiviral effects on reducing hospitalization and death, and potential antiviral effects on reducing transmission. For each country, we varied daily treatment initiation rate (DTIR) and antiviral effect in reducing transmission (AVT). RESULTS: Irrespective of location and AVT, widespread antiviral treatment of symptomatic adult infections (20% DTIR) prevented the majority of COVID-19 deaths, and recruiting 6% of all adult symptomatic infections daily reduced mortality by over 20% in all countries. Furthermore, our model projected that targeting antiviral treatment to the oldest age group (65 years old and older, DTIR of 20%) can prevent over 30% of deaths. Our results suggest that early antiviral treatment (as soon as possible after inception of infection) is needed to mitigate transmission, preventing 50% more infections compared to late treatment (started 3 to 5 days after symptoms onset). Our results highlight the synergistic effect of vaccination and antiviral treatment: as the vaccination rate increases, antivirals have a larger relative impact on population transmission. Finally, our model projects that even in highly vaccinated populations, adding antiviral treatment can be extremely helpful to mitigate COVID-19 deaths. CONCLUSIONS: These results suggest that antiviral treatments can become a strategic tool that, in combination with vaccination, can significantly reduce COVID-19 hospitalizations and deaths and can help control SARS-CoV-2 transmission.

Improving vaccination coverage and offering vaccine to all school-age children allowed uninterrupted in-person schooling in King County, WA: Modeling analysis.

The rapid spread of highly transmissible SARS-CoV-2 variants combined with slowing pace of vaccination in Fall 2021 created uncertainty around the future trajectory of the epidemic in King County, Washington, USA. We analyzed the benefits of offering vaccination to children ages 5-11 and expanding the overall vaccination coverage using mathematical modeling. We adapted a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington, to simulate scenarios of vaccinating children aged 5-11 with different starting dates and different proportions of physical interactions (PPI) in schools being restored. Dynamic social distancing was implemented in response to changes in weekly hospitalizations. Reduction of hospitalizations and estimated time under additional social distancing measures are reported over the 2021-2022 school year. In the scenario with 85% vaccination coverage of 12+ year-olds, offering early vaccination to children aged 5-11 with 75% PPI was predicted to prevent 756 (median, IQR 301-1434) hospitalizations cutting youth hospitalizations in half compared to no vaccination and largely reducing the need for additional social distancing measures over the school year. If, in addition, 90% overall vaccination coverage was reached, 60% of remaining hospitalizations would be averted and the need for increased social distancing would almost certainly be avoided. Our work suggests that uninterrupted in-person schooling in King County was partly possible because reasonable precaution measures were taken at schools to reduce infectious contacts. Rapid vaccination of all school-aged children provides meaningful reduction of the COVID-19 health burden over this school year but only if implemented early. It remains critical to vaccinate as many people as possible to limit the morbidity and mortality associated with future epidemic waves.

Optimizing one-dose and two-dose cholera vaccine allocation in outbreak settings: A modeling study.

BACKGROUND: A global stockpile of oral cholera vaccine (OCV) was established in 2013 for use in outbreak response and are licensed as two-dose regimens. Vaccine availability, however, remains limited. Previous studies have found that a single dose of OCV may provide substantial protection against cholera. METHODS: Using a mathematical model with two age groups paired with optimization algorithms, we determine the optimal vaccination strategy with one and two doses of vaccine to minimize cumulative overall infections, symptomatic infections, and deaths. We explore counterfactual vaccination scenarios in three distinct settings: Maela, the largest refugee camp in Thailand, with high in- and out-migration; N'Djamena, Chad, a densely populated region; and Haiti, where departments are connected by rivers and roads. RESULTS: Over the short term under limited vaccine supply, the optimal strategies for all objectives prioritize one dose to the older age group (over five years old), irrespective of setting and level of vaccination coverage. As more vaccine becomes available, it is optimal to administer a second dose for long-term protection. With enough vaccine to cover the whole population with one dose, the optimal strategies can avert up to 30% to 90% of deaths and 36% to 92% of symptomatic infections across the three settings over one year. The one-dose optimal strategies can avert 1.2 to 1.8 times as many cases and deaths compared to the standard two-dose strategy. CONCLUSIONS: In an outbreak setting, speedy vaccination campaigns with a single dose of OCV is likely to avert more cases and deaths than a two-dose pro-rata campaign under a limited vaccine supply.

Could widespread use of antiviral treatment curb the COVID-19 pandemic? A modeling study.

Despite the development of safe and effective vaccines, effective treatments for COVID-19 disease are still desperately needed. Recently, two antiviral drugs have shown to be effective in reducing hospitalizations in clinical trials. In the present work, we use an agent-based mathematical model to assess the potential population impact of the use of antiviral treatments in four countries, corresponding to four current levels of vaccination coverage: Kenya, Mexico, United States (US) and Belgium, with 1.5, 38, 57 and 74% of their populations vaccinated. For each location, we varied antiviral coverage and antiviral effect in reducing viral load (25, 50, 75 or 100% reduction). Irrespective of location, widespread antiviral treatment of symptomatic infections (≥50% coverage) is expected to prevent the majority of COVID-19 deaths. Furthermore, even treating 20% of adult symptomatic infections, is expected to reduce mortality by a third in all countries, irrespective of the assumed treatment efficacy in reducing viral load. Our results suggest that early antiviral treatment is needed to mitigate transmission, with early treatment (within two days of symptoms) preventing 50% more infections compared to late treatment (started on days 3 to 5 after developing symptoms). Our results highlight the synergistic effect of vaccination and antiviral treatment: as vaccination rate increased, antiviral treatment had a bigger impact on overall transmission. These results suggest that antiviral treatments can become a strategic tool that, in combination with vaccination, can significantly control SASRS-CoV-2 transmission and reduce COVID-19 hospitalizations and deaths.

Quantifying the Impact of Lifting Community Nonpharmaceutical Interventions for COVID-19 During Vaccination Rollout in the United States.

Using a mathematical model, we estimated the potential impact on mortality and total infections of completely lifting community nonpharmaceutical interventions when only a small proportion of the population has been fully vaccinated in 2 states in the United States. Lifting all community nonpharmaceutical interventions immediately is predicted to result in twice as many deaths over the next 6 months as a more moderate reopening allowing 70% of prepandemic contacts.

COVID-19 vaccines that reduce symptoms but do not block infection need higher coverage and faster rollout to achieve population impact.

Trial results for two COVID-19 vaccines suggest at least 90% efficacy against symptomatic disease (VEDIS). It remains unknown whether this efficacy is mediated by lowering SARS-CoV-2 infection susceptibility (VESUSC) or development of symptoms after infection (VESYMP). We aim to assess and compare the population impact of vaccines with different efficacy profiles (VESYMP and VESUSC) satisfying licensure criteria. We developed a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington. Rollout scenarios starting December 2020 were simulated with combinations of VESUSC and VESYMP resulting in up to 100% VEDIS. We assumed no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported. Rollouts of 1 M vaccinations (5000 daily) using vaccines with 50% VEDIS are projected to prevent 23-46% of infections and 31-46% of deaths over 1 year. In comparison, vaccines with 90% VEDIS are projected to prevent 37-64% of infections and 46-64% of deaths over 1 year. In both cases, there is a greater reduction if VEDIS is mediated mostly by VESUSC. The use of a "symptom reducing" vaccine will require twice as many people vaccinated than a "susceptibility reducing" vaccine with the same 90% VEDIS to prevent 50% of the infections and death over 1 year. Delaying the start of the vaccination by 3 months decreases the expected population impact by more than 50%. Vaccines which prevent COVID-19 disease but not SARS-CoV-2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.

Optimizing vaccine allocation for COVID-19 vaccines shows the potential role of single-dose vaccination.

Most COVID-19 vaccines require two doses, however with limited vaccine supply, policymakers are considering single-dose vaccination as an alternative strategy. Using a mathematical model combined with optimization algorithms, we determined optimal allocation strategies with one and two doses of vaccine under various degrees of viral transmission. Under low transmission, we show that the optimal allocation of vaccine vitally depends on the single-dose efficacy. With high single-dose efficacy, single-dose vaccination is optimal, preventing up to 22% more deaths than a strategy prioritizing two-dose vaccination for older adults. With low or moderate single-dose efficacy, mixed vaccination campaigns with complete coverage of older adults are optimal. However, with modest or high transmission, vaccinating older adults first with two doses is best, preventing up to 41% more deaths than a single-dose vaccination given across all adult populations. Our work suggests that it is imperative to determine the efficacy and durability of single-dose vaccines, as mixed or single-dose vaccination campaigns may have the potential to contain the pandemic much more quickly.

Protection afforded by previous Vibrio cholerae infection against subsequent disease and infection: A review.

BACKGROUND: Cholera is an acute, diarrheal disease caused by Vibrio cholerae O1 or 139 that is associated with a high global burden. METHODS: We analyzed the estimated duration of immunity following cholera infection from available published studies. We searched PubMed and Web of Science for studies of the long-term immunity following cholera infection. We identified 22 eligible studies and categorized them as either observational, challenge, or serological. RESULTS: We found strong evidence of protection at 3 years after infection in observational and challenge studies. However, serological studies show that elevated humoral markers of potential correlates of protection returned to baseline within 1 year. Additionally, a subclinical cholera infection may confer lower protection than a clinical one, as suggested by 3 studies that found that, albeit with small sample sizes, most participants with a subclinical infection from an initial challenge with cholera had a symptomatic infection when rechallenged with a homologous biotype. CONCLUSIONS: This review underscores the need to elucidate potential differences in the protection provided by clinical and subclinical cholera infections. Further, more studies are warranted to bridge the gap between the correlates of protection and cholera immunity. Understanding the duration of natural immunity to cholera can help guide control strategies and policy.

Optimizing vaccine allocation for COVID-19 vaccines: potential role of single-dose vaccination.

Most COVID-19 vaccines require two doses, however with limited vaccine supply, policymakers are considering single-dose vaccination as an alternative strategy. Using a mathematical model combined with optimization algorithms, we determined optimal allocation strategies with one and two doses of vaccine under various degrees of viral transmission. Under low transmission, we show that the optimal allocation of vaccine vitally depends on the single-dose efficacy (SDE). With high SDE, single-dose vaccination is optimal, preventing up to 22% more deaths than a strategy prioritizing two-dose vaccination for older adults. With low or moderate SDE, mixed vaccination campaigns with complete coverage of older adults are optimal. However, with modest or high transmission, vaccinating older adults first with two doses is best, preventing up to 41% more deaths than a single-dose vaccination given across all adult populations. Our work suggests that it is imperative to determine the efficacy and durability of single-dose vaccines, as mixed or single-dose vaccination campaigns may have the potential to contain the pandemic much more quickly.

Vaccine optimization for COVID-19: who to vaccinate first?

A vaccine, when available, will likely become our best tool to control the current COVID-19 pandemic. Even in the most optimistic scenarios, vaccine shortages will likely occur. Using an age-stratified mathematical model paired with optimization algorithms, we determined optimal vaccine allocation for four different metrics (deaths, symptomatic infections, and maximum non-ICU and ICU hospitalizations) under many scenarios. We find that a vaccine with effectiveness ≥50% would be enough to substantially mitigate the ongoing pandemic provided that a high percentage of the population is optimally vaccinated. When minimizing deaths, we find that for low vaccine effectiveness, irrespective of vaccination coverage, it is optimal to allocate vaccine to high-risk (older) age-groups first. In contrast, for higher vaccine effectiveness, there is a switch to allocate vaccine to high-transmission (younger) age-groups first for high vaccination coverage. While there are other societal and ethical considerations, this work can provide an evidence-based rationale for vaccine prioritization.

Achieving coordinated national immunity and cholera elimination in Haiti through vaccination: a modelling study.

BACKGROUND: Cholera was introduced into Haiti in 2010. Since then, more than 820 000 cases and nearly 10 000 deaths have been reported. Oral cholera vaccine (OCV) is safe and effective, but has not been seen as a primary tool for cholera elimination due to a limited period of protection and constrained supplies. Regionally, epidemic cholera is contained to the island of Hispaniola, and the lowest numbers of cases since the epidemic began were reported in 2019. Hence, Haiti may represent a unique opportunity to eliminate cholera with OCV. METHODS: In this modelling study, we assessed the probability of elimination, time to elimination, and percentage of cases averted with OCV campaign scenarios in Haiti through simulations from four modelling teams. For a 10-year period from January 19, 2019, to Jan 13, 2029, we compared a no vaccination scenario with five OCV campaign scenarios that differed in geographical scope, coverage, and rollout duration. Teams used weekly department-level reports of suspected cholera cases from the Haiti Ministry of Public Health and Population to calibrate the models and used common vaccine-related assumptions, but other model features were determined independently. FINDINGS: Among campaigns with the same vaccination coverage (70% fully vaccinated), the median probability of elimination after 5 years was 0-18% for no vaccination, 0-33% for 2-year campaigns focused in the two departments with the highest historical incidence, 0-72% for three-department campaigns, and 35-100% for nationwide campaigns. Two-department campaigns averted a median of 12-58% of infections, three-department campaigns averted 29-80% of infections, and national campaigns averted 58-95% of infections. Extending the national campaign to a 5-year rollout (compared to a 2-year rollout), reduced the probability of elimination to 0-95% and the proportion of cases averted to 37-86%. INTERPRETATION: Models suggest that the probability of achieving zero transmission of Vibrio cholerae in Haiti with current methods of control is low, and that bolder action is needed to promote elimination of cholera from the region. Large-scale cholera vaccination campaigns in Haiti would offer the opportunity to synchronise nationwide immunity, providing near-term population protection while improvements to water and sanitation promote long-term cholera elimination. FUNDING: Bill & Melinda Gates Foundation, Global Good Fund, Institute for Disease Modeling, Swiss National Science Foundation, and US National Institutes of Health.

Evaluating the Effectiveness of Social Distancing Interventions to Delay or Flatten the Epidemic Curve of Coronavirus Disease.

By April 2, 2020, >1 million persons worldwide were infected with severe acute respiratory syndrome coronavirus 2. We used a mathematical model to investigate the effectiveness of social distancing interventions in a mid-sized city. Interventions reduced contacts of adults >60 years of age, adults 20-59 years of age, and children <19 years of age for 6 weeks. Our results suggest interventions started earlier in the epidemic delay the epidemic curve and interventions started later flatten the epidemic curve. We noted that, while social distancing interventions were in place, most new cases, hospitalizations, and deaths were averted, even with modest reductions in contact among adults. However, when interventions ended, the epidemic rebounded. Our models suggest that social distancing can provide crucial time to increase healthcare capacity but must occur in conjunction with testing and contact tracing of all suspected cases to mitigate virus transmission.

Vaccine optimization for COVID-19: Who to vaccinate first?

Vaccines, when available, will likely become our best tool to control the COVID-19 pandemic. Even in the most optimistic scenarios, vaccine shortages will likely occur. Using an age-stratified mathematical model paired with optimization algorithms, we determined optimal vaccine allocation for four different metrics (deaths, symptomatic infections, and maximum non-ICU and ICU hospitalizations) under many scenarios. We find that a vaccine with effectiveness ≥50% would be enough to substantially mitigate the ongoing pandemic, provided that a high percentage of the population is optimally vaccinated. When minimizing deaths, we find that for low vaccine effectiveness, irrespective of vaccination coverage, it is optimal to allocate vaccine to high-risk (older) age groups first. In contrast, for higher vaccine effectiveness, there is a switch to allocate vaccine to high-transmission (younger) age groups first for high vaccination coverage. While there are other societal and ethical considerations, this work can provide an evidence-based rationale for vaccine prioritization.

Successes and Failures of the Live-attenuated Influenza Vaccine: Can We Do Better?

BACKGROUND: The effectiveness of the live-attenuated influenza vaccine (LAIV) can vary widely, ranging from 0% to 50%. The reasons for these discrepancies remain largely unclear. METHODS: We use mathematical models to explore how the efficacy of LAIV is affected by the degree of mismatch with the currently circulating influenza strain and interference with pre-existing immunity. The models incorporate 3 key antigenic distances: the distances between the vaccine strain, pre-existing immunity, and the challenge strain. RESULTS: Our models show that an LAIV that is matched with the currently circulating strain is likely to have only modest efficacy. Our results suggest that the efficacy of the vaccine would be increased (optimized) if, rather than being matched to the circulating strain, it is antigenically slightly further from pre-existing immunity than the circulating strain. The models also suggest 2 regimes in which LAIV that is matched to circulating strains may be protective: in children before they have built immunity to circulating strains and in response to novel strains (such as antigenic shifts) which are at substantial antigenic distance from previously circulating strains. We provide an explanation for the variation in vaccine effectiveness between studies and countries of vaccine effectiveness observed during the 2014-2015 influenza season. CONCLUSIONS: LAIV is offered to children across the world; however, its effectiveness significantly varies between studies. Here, we propose a mechanistic explanation to understand these differences. We further propose a way to select the LAIV strain that would have a higher chance of being protective.