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Declines in vaccination coverage for vaccine-preventable diseases, such as measles and chickenpox, have enabled their surprising comebacks and pose significant public health challenges in the wake of growing vaccine hesitancy. Vaccine opt-outs and refusals are often fueled by beliefs concerning perceptions of vaccine effectiveness and exaggerated risks. Here, we quantify the impact of competing beliefs -- vaccine-averse versus vaccine-neutral -- on social imitation dynamics of vaccination, alongside the epidemiological dynamics of disease transmission. These beliefs may be pre-existing and fixed, or coevolving attitudes. This interplay among beliefs, behaviors, and disease dynamics demonstrates that individuals are not perfectly rational; rather, they base their vaccine uptake decisions on beliefs, personal experiences, and social influences. We find that the presence of a small proportion of fixed vaccine-averse beliefs can significantly exacerbate the vaccination dilemma, making the tipping point in the hysteresis loop more sensitive to changes in individuals' perceived costs of vaccination and vaccine effectiveness. However, in scenarios where competing beliefs spread concurrent

Effective and efficient scheduling of vaccine distribution can significantly impact vaccine uptake, which is critical to controlling the spread of infectious diseases. Ineffective scheduling can lead to waste, delays, and low vaccine coverage, potentially weakening the efforts to protect the public. Organizations such as UNICEF (United Nations Children's Fund), PAHO (Pan American Health Organization), and GAVI (Gavi, the Vaccine Alliance) coordinate vaccine tenders to ensure that enough supply is available on the international market at the lowest possible prices. Scheduling vaccine tenders over a planning horizon in a way that is equitable, efficient, and accessible is a complex problem that involves trade-offs between multiple objectives while ensuring that vaccine availability, demand, and logistical constraints are met. The current method for scheduling tenders is generally reactive and over short planning horizons. Vaccine tenders are scheduled when supply is insufficient to cover demand. We propose an optimization model to dynamically and proactively generate vaccine tender schedules over long planning horizons. This model helps us address the following research questions: Wh

Background: The Cox model and its extensions assuming proportional hazards is widely used to estimate vaccine efficacy (VE). In the typical situation that VE wanes over time, the VE estimates are not only sensitive to study duration and timing of vaccine delivery in relation to disease seasonality but also biased in the presence of sample attrition. Furthermore, estimates of vaccine impact such as number of cases averted (NCA) are sensitive to background disease incidence and timing of vaccine delivery. Comparison of the estimates between trials with different features can be misleading. Methods: We propose estimation of VE as a function of time in the Cox model framework, using the area under the VE curve as a summary measure of VE, and extension of the method to estimate vaccine impact. We use simulations and re-analysis of a RTS,S/AS01 malaria vaccine trial dataset to demonstrate their properties and applications. Results: Simulation under scenarios with different trial duration, magnitude of sample attrition and timing of vaccine delivery, all assuming vaccine protection wanes over time, demonstrated the problems of conventional methods assuming proportional hazard, robustness

To design effective vaccine policies, policymakers need detailed data about who has been vaccinated, who is holding out, and why. However, existing data in the US are insufficient: reported vaccination rates are often delayed or missing, and surveys of vaccine hesitancy are limited by high-level questions and self-report biases. Here, we show how large-scale search engine logs and machine learning can be leveraged to fill these gaps and provide novel insights about vaccine intentions and behaviors. First, we develop a vaccine intent classifier that can accurately detect when a user is seeking the COVID-19 vaccine on search. Our classifier demonstrates strong agreement with CDC vaccination rates, with correlations above 0.86, and estimates vaccine intent rates to the level of ZIP codes in real time, allowing us to pinpoint more granular trends in vaccine seeking across regions, demographics, and time. To investigate vaccine hesitancy, we use our classifier to identify two groups, vaccine early adopters and vaccine holdouts. We find that holdouts, compared to early adopters matched on covariates, are 69% more likely to click on untrusted news sites. Furthermore, we organize 25,000 va

Knowing whether vaccine protection wanes over time is important for health policy and drug development. However, quantifying waning effects is difficult. A simple contrast of vaccine efficacy at two different times compares different populations of individuals: those who were uninfected at the first time versus those who remain uninfected until the second time. Thus, the contrast of vaccine efficacy at early and late times can not be interpreted as a causal effect. We propose to quantify vaccine waning using the challenge effect, which is a contrast of outcomes under controlled exposures to the infectious agent following vaccination. We identify sharp bounds on the challenge effect under non-parametric assumptions that are broadly applicable in vaccine trials using routinely collected data. We demonstrate that the challenge effect can differ substantially from the conventional vaccine efficacy due to depletion of susceptible individuals from the risk set over time. Finally, we apply the methods to derive bounds on the waning of the BNT162b2 COVID-19 vaccine using data from a placebo-controlled randomized trial. Our estimates of the challenge effect suggest waning protection after 2

Vaccine randomized trials are typically designed to be blinded, ensuring that the estimated vaccine efficacy (VE) reflects the immunological effect of the vaccine. When blinding is broken, however, the estimated VE reflects not only the immunological effect but also behavioral effects stemming from participants' awareness of their treatment status. Recent work has proposed alternative causal estimands to the standard VE to address this issue, but their point identification results require a strong assumption: the absence of unmeasured common causes of infection risk and participants' belief about whether they received the vaccine. Personality traits, for example, may plausibly violate this assumption. We relax this assumption and derive nonparametric causal bounds for different types of VE. We construct these bounds using two approaches: linear programming-based and monotonicity-based methods. We further consider several possible causal structures for vaccine trials and show how the nonparametric bounds differ across these scenarios. Finally, we illustrate the performance of the proposed bounds using fully synthetic data and a semi-synthetic data example based on a COVID-19 vaccine

Many countries have secured larger quantities of COVID-19 vaccines than their populace is willing to take. This abundance and variety of vaccines created a historical moment to understand vaccine hesitancy better. Never before were more types of vaccines available for an illness and the intensity of vaccine-related public discourse is unprecedented. Yet, the heterogeneity of hesitancy by vaccine types has been neglected so far, even though factual or believed vaccine characteristics and patient attributes are known to influence acceptance. We address this problem by analysing acceptance and assessment of five vaccine types using information collected with a nationally representative survey at the end of the third wave of the COVID-19 pandemic in Hungary, where a unique portfolio of vaccines were available to the public in large quantities. Our special case enables us to quantify revealed preferences across vaccine types since one could evaluate a vaccine unacceptable and even could reject an assigned vaccine to wait for another type. We find that the source of information that respondents trust characterizes their attitudes towards vaccine types differently and leads to divergent v

The global SARS-CoV-2 (COVID-19) pandemic highlighted the challenge of equitable vaccine distribution between high- and low-income countries. Many high-income countries were reluctant or slow to distribute extra doses of the vaccine to lower-income countries via the COVID-19 Vaccines Global Access (COVAX) collaboration. In addition to moral objections to such vaccine nationalism, vaccine inequity during a pandemic could contribute to the evolution of new variants of the virus and possibly increase total deaths, including in the high-income countries. Using the COVID-19 pandemic as a case study, we use the epidemiological model of Holleran et al. that incorporates virus mutation. We identify realistic scenarios under which a donor country prefers to donate vaccines before distributing them locally in order to minimize local deaths during a pandemic. We demonstrate that a nondonor-first vaccination policy can delay, sometimes dramatically, the emergence of more-contagious variants. Even more surprising, donating all vaccines is sometimes better for the donor country than a sharing policy in which half of the vaccines are donated and half are retained because of the impact donation ca

Vaccine effectiveness (VE) is typically defined as incidence rate ratio, cumulative-risk ratio, or odds ratio. The VE based on incidence rate ratio is known to be time-invariant over the study period for leaky action vaccines and, the VE based on cumulative-risk ratio is time-invariant for all-or-none action vaccines. Consequently, these VE measures are recommended as appropriate measures of VE for leaky and all-or-none vaccines, respectively. However, in diseases with multiple pathogen variants and multiple vaccines, investigators may also be interested in variant-specific VE of a vaccine, the relative VE of a vaccine against two variants, or the relative VE of different vaccines against a given variant. In this multi-variant and multi-vaccine scenario, the temporal properties of the aforementioned VE measures have not been studied entirely yet. Furthermore, no general-purpose sample size calculator is available for either studies that intend to estimate variant-specific VE or relative VE. As a solution, we define variant-specific and relative VE measures while accounting for multiple competing pathogen variants. We then propose a generic mode of action for all-or-none vaccines in

Purpose: Only few companies were able to produce vaccine again COVID-19. Thus, one producer supplied it to many countries. The distribution was not effective. Some countries overstocked the vaccine while other countries were not able to buy enough. The purpose of the present paper is to provide with a frame such that one producer distributes the vaccine to a set of countries in a way that the shortage is minimized. Methodology: The consumption of the countries are approximated by regression functions taking into account the saturation of the process. The distribution of the vaccine is determined by MIP models of operations research. Findings: Effective distribution of vaccine can be obtained for even a large number of countries. Both the level of the shortage and the number of the consecutive shortage days in a country can be controlled. Practical implications: A group of countries can act as a single partner of a pharmaceutical company. They can get a steady supply. The company gets a well-organized delivery plan. Social implications: More people can be saved because of the steady supply of the vaccine. Originality: The paper develops a new concept for the fair distribution of vac

Background Advances in machine learning (ML) models have increased the capability of researchers to detect vaccine hesitancy in social media using Natural Language Processing (NLP). A considerable volume of research has identified the persistence of COVID-19 vaccine hesitancy in discourse shared on various social media platforms. Methods Our objective in this study was to conduct a systematic review of research employing sentiment analysis or stance detection to study discourse towards COVID-19 vaccines and vaccination spread on Twitter (officially known as X since 2023). Following registration in the PROSPERO international registry of systematic reviews, we searched papers published from 1 January 2020 to 31 December 2023 that used supervised machine learning to assess COVID-19 vaccine hesitancy through stance detection or sentiment analysis on Twitter. We categorized the studies according to a taxonomy of five dimensions: tweet sample selection approach, self-reported study type, classification typology, annotation codebook definitions, and interpretation of results. We analyzed if studies using stance detection report different hesitancy trends than those using sentiment analysi

Over the past 150 years, vaccines have revolutionized the relationship between people and disease. During the COVID-19 pandemic, technologies such as mRNA vaccines have received attention due to their novelty and successes. However, more traditional vaccine development platforms have also yielded important tools in the worldwide fight against the SARS-CoV-2 virus. A variety of approaches have been used to develop COVID-19 vaccines that are now authorized for use in countries around the world. In this review, we highlight strategies that focus on the viral capsid and outwards, rather than on the nucleic acids inside. These approaches fall into two broad categories: whole-virus vaccines and subunit vaccines. Whole-virus vaccines use the virus itself, either in an inactivated or attenuated state. Subunit vaccines contain instead an isolated, immunogenic component of the virus. Here, we highlight vaccine candidates that apply these approaches against SARS-CoV-2 in different ways. In a companion manuscript, we review the more recent and novel development of nucleic-acid based vaccine technologies. We further consider the role that these COVID-19 vaccine development programs have played

Despite the unprecedented success in the rapid development of several effective vaccines against the Cov-SARS-2, global vaccination rollout efforts suffer from vaccine distribution inequality and vaccine acceptance, leading to insufficient public immunity provided by the vaccine products. While a major current focus in vaccine acceptance research is how to model and inform vaccine acceptance based on social-demographic parameters, characteristics of vaccine acceptance are not well understood and in particular, it is not known whether and how information diffusion influences vaccine acceptance. This study examines how information diffusion can change vaccine acceptance by developing a comprehensive computational model with an agent-based simulation technique to overcome the modeling and quantification complexity associated with socio-demographics, vaccine types, population statistics, and information diffusion. Our analyses, calibrated by the vaccine acceptance survey data from the provinces and territories of Canada, provide clear evidence that the propagation of information can greatly influence vaccine acceptance rates. The results illustrate that spread of negative messages abou

Traditional measures of vaccine efficacy (VE) are inherently asymmetric, constrained above by $1$ but unbounded below. As a result, VE estimates and corresponding confidence intervals can extend far below zero, making interpretation difficult and potentially obscuring whether the apparent effect reflects true harm or simply statistical uncertainty. The proposed symmetric vaccine efficacy (SVE) is a bounded and interpretable alternative to VE that maintains desirable statistical properties while resolving these asymmetries. SVE is defined as a symmetric transformation of infection risks, with possible values within $[-1, 1]$, providing a common scale for both beneficial and harmful vaccine effects. This paper describes the relationship between SVE and traditional VE, considers inference about SVE, and illustrates the utility of the proposed measure by reanalyzing data from a randomized trial of a candidate HIV vaccine. Open-source tools for computing estimates of SVE and corresponding confidence intervals are available in R through the sve package.

We model the impact of local vaccine mandates on the spread of vaccine-preventable infectious diseases, which in the absence of vaccines will mainly affect children. Examples of such diseases are measles, rubella, mumps and pertussis. To model the spread of the pathogen, we use a stochastic SIR (Susceptible, Infectious, Recovered) model with two levels of mixing in a closed population, often referred to as the household model. In this model individuals make local contacts within a specific small subgroup of the population (e.g.\ within a household or a school class), while they also make global contacts with random people in the population at a much lower rate than the rate of local contacts. We consider what happens if schools are given freedom to impose vaccine mandates on all of their pupils, except for the pupils that are exempt from vaccination because of medical reasons. We investigate how such a mandate affects the probability of an outbreak of a disease and the probability that a pupil that is medically exempt from vaccination, gets infected during an outbreak. We show that if the population vaccine coverage is close to the herd-immunity level then both probabilities may in

As observed during the COVID-19 pandemic, high-income countries, such as the U.S., may exhibit vaccine nationalism during a pandemic: stockpiling doses of vaccine for their own citizens and being reluctant to distribute doses of the vaccine to lower-income countries. While many cite moral objections to vaccine nationalism, vaccine inequity during a pandemic could possibly worsen the global effects of the pandemic, including in the high-income countries themselves, through the evolution of new variants of the virus. This paper uses the COVID-19 pandemic as a case study to identify scenarios under which it might be in a high-income nation's own interest to donate vaccine doses to another country before its own population has been fully vaccinated. We develop an extended SEIR (susceptible-exposed-infectious-recovered) epidemiological model embedded in an optimization framework and examine scenarios involving a single donor and multiple recipient (nondonor) geographic areas. We find that policies other than donor-first can delay the emergence of a more-contagious variant compared to donor-first, sometimes reducing donor-country deaths in addition to total deaths. Thus, vaccine distribu

A vaccine passport serves as documentary proof, providing passport holders with greater freedom while roaming around during pandemics. It confirms vaccination against certain infectious diseases like COVID-19, Ebola, and flu. The key challenges faced by the digital vaccine passport system include passport forgery, unauthorized data access, and inaccurate information input by vaccination centers. Privacy concerns also need to be addressed to ensure that the user's personal identification information (PII) is not compromised. Additionally, it is necessary to track vaccine vials or doses to verify their authenticity, prevent misuse and illegal sales, as well as to restrict the illicit distribution of vaccines. To address these challenges, we propose a Blockchain-Enabled Secure Vaccine Passport System, leveraging the power of smart contracts. Our solution integrates off-chain and on-chain cryptographic computations, facilitating secure communication among various entities. We have utilized the InterPlanetary File System (IPFS) to store encrypted vaccine passports of citizens securely. Our prototype is built on the Ethereum platform, with smart contracts deployed on the Sepolia Test net

Background: Despite lacking scientific support, vaccine hesitancy is widespread. While vaccine damage as a scientific fact is statistically highly uncommon, emerging social and technological forces have converted probable vaccine damage into an alternative fact. Methods: Using the Eurobarometer 91.2 survey on a statistically representative EU27-UK sample interviewed in March 2019, we documented perceptions of vaccine risks and identified three belief configurations regarding vaccine effectiveness, safety, and usefulness, through exploratory cluster analysis. Results: The public beliefs in vaccine risks are frequent. Approximatively one-tenth of the EU27-UK population consider vaccines are not rigorously tested before authorization, one-third believe vaccines can overload or weaken the immune system and that they can cause the disease against which they protect, and almost one-half believe vaccines can cause serious side effects. We identified three belief configurations: the skeptical, the confident, and the trade-off clusters. The skeptical type (approx. 11 percent of EU27-UK respondents) is defined by the belief that vaccines are rather ineffective, affected by risks of probable

Mass vaccination remains a long-lasting challenge for disease control and prevention with upticks in vaccine hesitancy worldwide. Here, we introduce an experience-based learning (Q-learning) dynamics model of vaccination behavior in social networks, where agents choose whether or not to vaccinate given environmental feedbacks from their local neighborhood. We focus on how bounded rationality of individuals impacts decision-making of irrational agents in networks. Additionally, we observe hysteresis behavior and bistability with respect to vaccination cost and the Q-learning hyperparameters such as discount rate. Our results offer insight into the complexities of Q-learning and particularly how foresightedness of individuals will help mitigate - or conversely deteriorate, therefore acting as a double-edged sword - collective action problems in important contexts like vaccination. We also find a diversification of uptake choices, with individuals evolving into complete opt-in vs. complete opt-out. Our results have real-world implications for targeting the persistence of vaccine hesitancy using an interdisciplinary computational social science approach integrating social networks, gam