Browsing by Subject "Vaccines"
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Item A Comparative Analysis of Influenza Vaccination Programs(Public Library of Science, 2006-10-03) Bansal, Shweta; Pourbohloul, Babak; Meyers, Lauren AncelBackground -- The threat of avian influenza and the 2004–2005 influenza vaccine supply shortage in the United States have sparked a debate about optimal vaccination strategies to reduce the burden of morbidity and mortality caused by the influenza virus. Methods and Findings -- We present a comparative analysis of two classes of suggested vaccination strategies: mortality-based strategies that target high-risk populations and morbidity-based strategies that target high-prevalence populations. Applying the methods of contact network epidemiology to a model of disease transmission in a large urban population, we assume that vaccine supplies are limited and then evaluate the efficacy of these strategies across a wide range of viral transmission rates and for two different age-specific mortality distributions. We find that the optimal strategy depends critically on the viral transmission level (reproductive rate) of the virus: morbidity-based strategies outperform mortality-based strategies for moderately transmissible strains, while the reverse is true for highly transmissible strains. These results hold for a range of mortality rates reported for prior influenza epidemics and pandemics. Furthermore, we show that vaccination delays and multiple introductions of disease into the community have a more detrimental impact on morbidity-based strategies than mortality-based strategies. Conclusions -- If public health officials have reasonable estimates of the viral transmission rate and the frequency of new introductions into the community prior to an outbreak, then these methods can guide the design of optimal vaccination priorities. When such information is unreliable or not available, as is often the case, this study recommends mortality-based vaccination priorities.Item Economic evaluation of using adenovirus type 4 and type 7 vaccines in United States military basic trainees(2014-05) Vazquez, Meredith Hodges; Wilson, James P.Adenoviruses, particularly types 4 and 7, are associated with febrile respiratory illness (FRI) outbreaks in US military basic trainees. Vaccines against these two serotypes controlled FRI in basic trainees until production ceased in the mid-1990s. After contracting a new manufacturer, adenovirus vaccination of military basic trainees resumed in 2011. The purpose of this dissertation was to assess the cost-effectiveness of using the new adenovirus type 4 and type 7 vaccines for the prevention of FRI in US military basic trainees from the perspective of each military branch. Two decision tree models comparing adenovirus vaccination to no adenovirus vaccination were used for this dissertation. The first model is similar to previous models used to assess the cost-effectiveness of the adenovirus vaccine in the military, where the outcome is number of FRI hospitalizations prevented. The second model created for this dissertation used information gathered from published literature and conversations with experts on the adenovirus vaccine. The outcome for the second model was number of training days lost (TDL) averted. Results from part I indicated that adenovirus vaccination of basic trainees was cost-effective as measured by FRI hospitalizations prevented in all US military service branches but the Coast Guard. The model showed that reintroducing the adenovirus vaccine to basic trainees saved the Army $5.8 million, the Navy, $1 million, the Marine Corps, $238,000, and the Air Force, $5.2 million, annually. In addition, adenovirus vaccination prevented 1,221, 543, 317, 677 cases of FRI hospitalization annually in the Army, Navy, Marine Corps, and Air Force respectively. In part II of this study, adenovirus vaccination of basic trainees was the dominant strategy as measured by TDL averted in all US military service branches but the Marine Corps and the Coast Guard. Results indicate that it would cost approximately $37.63 and $563.78 per TDL averted for the Marine Corps and Coast Guard respectively. Both models used for this dissertation provide evidence supporting the cost-effectiveness of using the adenovirus vaccine in US basic trainees in all services but the Coast Guard.Item Enhanced Protection against Ebola Virus Mediated by an Improved Adenovirus-Based Vaccine(Public Library of Science, 2009-04-23) Richardson, Jason S.; Yao, Michel K.; Tran, Kaylie N.; Croyle, Maria A.; Strong, James E.; Feldmann, Heinz; Kobinger, Gary P.Background -- The Ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. Currently, replication defective adenovirus-based Ebola vaccine is being studied in a phase I clinical trial. Another Ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to Ebola infection. In this report, we modified the common recombinant adenovirus serotype 5-based Ebola vaccine expressing the wild-type ZEBOV glycoprotein sequence from a CMV promoter (Ad-CMVZGP). The immune response elicited by this improved expression cassette vector (Ad-CAGoptZGP) and its ability to afford protection against lethal ZEBOV challenge in mice was compared to the standard Ad-CMVZGP vector. Methodology/Principal Findings -- Ad-CMVZGP was previously shown to protect mice, guinea pigs and nonhuman primates from an otherwise lethal challenge of Zaire ebolavirus. The antigenic expression cassette of this vector was improved through codon optimization, inclusion of a consensus Kozak sequence and reconfiguration of a CAG promoter (Ad-CAGoptZGP). Expression of GP from Ad-CAGoptZGP was substantially higher than from Ad-CMVZGP. Ad-CAGoptZGP significantly improved T and B cell responses at doses 10 to 100-fold lower than that needed with Ad-CMVZGP. Additionally, Ad-CAGoptZGP afforded full protections in mice against lethal challenge at a dose 100 times lower than the dose required for Ad-CMVZGP. Finally, Ad-CAGoptZGP induced full protection to mice when given 30 minutes post-challenge. Conclusions/Significance -- We describe an improved adenovirus-based Ebola vaccine capable of affording post-exposure protection against lethal challenge in mice. The molecular modifications of the new improved vaccine also translated in the induction of significantly enhanced immune responses and complete protection at a dose 100 times lower than with the previous generation adenovirus-based Ebola vaccine. Understanding and improving the molecular components of adenovirus-based vaccines can produce potent, optimized product, useful for vaccination and post-exposure therapy.Item Erratic Flu Vaccination Emerges from Short-Sighted Behavior in Contact Networks(Public Library of Science, 2011-01-27) Cornforth, Daniel M.; Reluga, Timothy C.; Shim, Eunha; Bauch, Chris T.; Galvani, Alison P.; Meyers, Lauren AncelThe effectiveness of seasonal influenza vaccination programs depends on individual-level compliance. Perceptions about risks associated with infection and vaccination can strongly influence vaccination decisions and thus the ultimate course of an epidemic. Here we investigate the interplay between contact patterns, influenza-related behavior, and disease dynamics by incorporating game theory into network models. When individuals make decisions based on past epidemics, we find that individuals with many contacts vaccinate, whereas individuals with few contacts do not. However, the threshold number of contacts above which to vaccinate is highly dependent on the overall network structure of the population and has the potential to oscillate more wildly than has been observed empirically. When we increase the number of prior seasons that individuals recall when making vaccination decisions, behavior and thus disease dynamics become less variable. For some networks, we also find that higher flu transmission rates may, counterintuitively, lead to lower (vaccine-mediated) disease prevalence. Our work demonstrates that rich and complex dynamics can result from the interaction between infectious diseases, human contact patterns, and behavior.Item The Impact of Imitation on Vaccination Behavior in Social Contact Networks(Public Library of Science, 2012-04-12) Ndeffo Mbah, Martial L.; Liu, Jingzhou; Bauch, Chris T.; Tekel, Yonas I.; Medlock, Jan; Meyers, Lauren Ancel; Galvani, Alison P.Previous game-theoretic studies of vaccination behavior typically have often assumed that populations are homogeneously mixed and that individuals are fully rational. In reality, there is heterogeneity in the number of contacts per individual, and individuals tend to imitate others who appear to have adopted successful strategies. Here, we use network-based mathematical models to study the effects of both imitation behavior and contact heterogeneity on vaccination coverage and disease dynamics. We integrate contact network epidemiological models with a framework for decision-making, within which individuals make their decisions either based purely on payoff maximization or by imitating the vaccination behavior of a social contact. Simulations suggest that when the cost of vaccination is high imitation behavior may decrease vaccination coverage. However, when the cost of vaccination is small relative to that of infection, imitation behavior increases vaccination coverage, but, surprisingly, also increases the magnitude of epidemics through the clustering of non-vaccinators within the network. Thus, imitation behavior may impede the eradication of infectious diseases. Calculations that ignore behavioral clustering caused by imitation may significantly underestimate the levels of vaccination coverage required to attain herd immunity.Item Influenza Vaccines: An Overview of the Most Common Seasonal Vaccination in the World(2018) Kartha, NiteshItem Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice(Public Library of Science, 2008-10-29) Croyle, Maria A.; Patel, Ami; Tran, Kaylie N.; Gray, Michael; Zhang, Yi; Strong, James E.; Feldmann, Heinz; Kobinger, Gary P.Pre-existing immunity to human adenovirus serotype 5 (Ad5) is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M.), nasal (I.N.) or oral (P.O.) route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP) fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-γ+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-γ+ CD8+ T cells (3.9±1% naïve vs. 3.6±1% pre-existing immunity, PEI) nor anti-Ebola neutralizing antibody (NAB, 40±10 reciprocal dilution, both groups). The number of INF-γ+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL) after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146±14, naïve vs. 120±16 SFC/million MNCs, PEI). However, pre-existing immunity reduced NAB levels in BAL by ~25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-γ+ CD8+ T cells 10 days after administration (0.3±0.3% PEG vs. 1.7±0.5% unmodified). PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine.Item Optimizing Tactics for Use of the U.S. Antiviral Strategic National Stockpile for Pandemic Influenza(Public Library of Science, 2011-01-19) Dimitrov, Nedialko B.; Goll, Sebastian; Hupert, Nathaniel; Pourbohloul, Babak; Meyers, Lauren AncelIn 2009, public health agencies across the globe worked to mitigate the impact of the swine-origin influenza A (pH1N1) virus. These efforts included intensified surveillance, social distancing, hygiene measures, and the targeted use of antiviral medications to prevent infection (prophylaxis). In addition, aggressive antiviral treatment was recommended for certain patient subgroups to reduce the severity and duration of symptoms. To assist States and other localities meet these needs, the U.S. Government distributed a quarter of the antiviral medications in the Strategic National Stockpile within weeks of the pandemic's start. However, there are no quantitative models guiding the geo-temporal distribution of the remainder of the Stockpile in relation to pandemic spread or severity. We present a tactical optimization model for distributing this stockpile for treatment of infected cases during the early stages of a pandemic like 2009 pH1N1, prior to the wide availability of a strain-specific vaccine. Our optimization method efficiently searches large sets of intervention strategies applied to a stochastic network model of pandemic influenza transmission within and among U.S. cities. The resulting optimized strategies depend on the transmissability of the virus and postulated rates of antiviral uptake and wastage (through misallocation or loss). Our results suggest that an aggressive community-based antiviral treatment strategy involving early, widespread, pro-rata distribution of antivirals to States can contribute to slowing the transmission of mildly transmissible strains, like pH1N1. For more highly transmissible strains, outcomes of antiviral use are more heavily impacted by choice of distribution intervals, quantities per shipment, and timing of shipments in relation to pandemic spread. This study supports previous modeling results suggesting that appropriate antiviral treatment may be an effective mitigation strategy during the early stages of future influenza pandemics, increasing the need for systematic efforts to optimize distribution strategies and provide tactical guidance for public health policy-makers.Item Using the theory of planned behavior to assess factors that influence the intent to use human papillomavirus (HPV) vaccine among young adult college students(2022-05-04) Orji, Chinelo Constance; Brown, Carolyn M., Ph. D.; Barner, Jamie; Moczygemba, Leticia; Morales-Campos, DaisyThe aim of this study was i.) to determine the salient beliefs college students have regarding HPV vaccination and ii.) to determine college students’ intentions to be fully vaccinated against HPV within 12 months and factors that influence their intention. The theory of planned behavior (TPB) served as the theoretical framework to guide the study. The study assessed the significance of each of the TPB constructs – attitude, subjective norms, and perceived behavioral control – as well as additional constructs – knowledge and religiosity – in predicting behavioral intention. The relationships between demographic/personal factors and the study constructs were also assessed. A mixed-methods study design including qualitative and quantitative components, was applied. The study sample was comprised of a convenience sample of college students aged between 18 to 45 years attending a large public university in central Texas. For the qualitative portion, three focus group sessions were carried out to elicit the beliefs regarding HPV vaccination. Two investigators conducted a content analysis of the qualitative data and reached consensus on coding discrepancies. Twenty-four students participated in the focus groups, and a total of 45 beliefs were identified. Of these, 18 were salient, including 6 behavioral beliefs, 6 normative beliefs, and 6 control beliefs. For the quantitative portion, a web-based survey was developed using the TPB and information identified from the focus groups. The survey was administered via Qualtrics. Data analyses comprised descriptive, bivariate, and multivariate methods. Covariate adjusted linear regression models were used to assess association between intention and study constructs. Of 438 students who participated in the survey, there were 213 usable surveys. The initial model with attitude, subjective norms and perceived behavioral control as predictors accounted for about 40 percent of the variance in intention (R²= 0.4046, p<0.0001). Attitude (b=0.58, p<0.0001) and subjective norms (b=0.15, p=0.0372) were significant predictors of intention, while perceived behavioral control (b=0.01, p=0.8982) was not. Provider recommendation was the only significant covariate (b=1.15, p=0.0386). The additional constructs knowledge (R²= 0.4018, p=0.8179) and religiosity (R²= 0.4026, p=0.5808) did not significantly contribute to the model. Attitude and subjective norms differed by several demographic and personal factors, namely age, gender, race/ethnicity, provider recommendation, STD screening, sexual history, and vaccine experience. This study supports the use of the TPB in identifying college students’ beliefs regarding HPV vaccination, and in predicting intention to get fully vaccinated against HPV in the next 12 months. A focus on attitude, subjective norms and provider recommendation may be useful in developing more suitable interventions. Future studies are needed to assess other factors that may influence intention in larger or different college populations.