Perfect Vaccine Research Articles

A game theoretic approach to discuss the positive secondary effect of vaccination scheme in an infinite and well-mixed population

Abstract Pre-emptive vaccination policy used in controlling the rapid spreading of infectious diseases is considered as one of the most challenging issues imposed to mankind, causing enormous death tolls over the years. This paper dedicatedly studies the dilemma effect coming from the failure of getting perfect immunity to those individuals who committed vaccination earlier. Therefore, we propose a new theoretical model that slows down the infection spreading and also facilitates quicker recovery time than what the previous model does even if a vaccinator fails to obtain perfect immunity. We name this effect as the “positive secondary effect” of vaccination as it gives a second chance to the vaccinators which in return subdues the rapid spreading that helps in producing better social average payoff as well as keeping the final epidemic size smaller. Moreover, to address the positive secondary effect more precisely, we introduce two different parameters; namely, relaxation parameter (η) and foster parameter (δ) in two different directions to quantify the individual effects resulting from each of the parameter space as well as their superposition effect. An in-depth discussion focuses on the influential role played by our proposed model via discounting and faster recovery effects while a second chance is given to the vaccinators. In addition, we also examine the situation when discounting effect brought by η outperforms very much than its faster recovery controlled by δ as well as the superposition effects. Unlike all previous studies dealing with vaccination game, we pay much attention to investigating the secondary effect of imperfect vaccination policy. Our proposed theoretical scheme completely reproduces the decision-making process of choosing an imperfect provision based on evolutionary game theory entailed with the widely used SIR (Susceptible–Infected–Recovered) epidemic model. Without considering any spatial structure and perfect vaccination policy, our model presumes the population being infinite and well-mixed to represent the infection spreading dynamics mathematically. This study is conducted throughout using the so-called theoretical approach. Besides that, three different updating rules based on evolutionary game theory have also been considered to investigate all possible situations. Later on, we draw 2D full phase diagrams showing the final epidemic size, vaccination coverage, and average social payoff quantitatively. Finally, our theoretical result is compared with the counterpart result obtained from the multi-agent simulation (MAS) approach and a good agreement is found, hence the appropriateness of the proposed model is fully justified.

Immunotherapy of Endothelin-1 Receptor Type A for Pulmonary Arterial Hypertension

BackgroundPulmonary arterial hypertension (PAH) is a chronic fatal disease. The treatment of PAH is less than ideal and the control is far from satisfactory worldwide. Vaccination provides a promising approach for treatment of PAH. ObjectivesThis study sought to find a vaccine against endothelin-1 (ET-1) receptor type A (ETAR) for treating PAH. MethodsThe ETRQβ-002 vaccine was screened and the specific antibodies against epitope ETR-002 belonging to the second extracellular loop of ETAR (including the polyclonal and monoclonal antibody) were produced. The effect of the antibodies on Ca2+-dependent signal transduction events was investigated. In vivo, ETRQβ-002 vaccine was used to vaccinate monocrotaline (MCT)- and Sugen/hypoxia–induced pulmonary hypertension animals. The monoclonal antibody (mAb) against ETR-002 was also injected into the PAH animals. The effect of ETRQβ-002 vaccine on pulmonary hypertension and remodeling of pulmonary arterioles and right ventricle (RV) was carefully evaluated. Further, the possible immune-mediated damage was detected in normal vaccinated animals. ResultsETR-002 peptide has perfect immunogenicity and ETRQβ-002 vaccine could induce strong antibody production. In vitro, the anti–ETR-002 antibody bound to ETAR and inhibited Ca2+-dependent signal transduction events, including extracellular signal-regulated kinase phosphorylation and elevation of intracellular Ca2+ concentration induced by ET-1. In vivo, both ETRQβ-002 vaccine and the mAb significantly decreased the RV systolic pressure up to 20 mm Hg and 10 mm Hg in MCT-exposed rats and Sugen/hypoxia–exposed mice, respectively. Also, ETRQβ-002 vaccine/mAb obviously ameliorated pathological remodeling of pulmonary arterioles and hypertrophy of the RV in PAH animals. Additionally, no significant immune-mediated damage was detected in vaccinated animals. ConclusionsETRQβ-002 vaccine/mAb attenuated remodeling of pulmonary arterioles and RV in MCT- and Sugen/hypoxia–induced PAH animals and decreased RV systolic pressure effectively through diminishing the pressure response and inhibiting signal transduction initiated by ET-1. ETRQβ-002 vaccine/mAb may provide a novel and promising method for PAH treatment.

SIR epidemics and vaccination on random graphs with clustering

In this paper we consider Susceptible rightarrow Infectious rightarrow Recovered (SIR) epidemics on random graphs with clustering. To incorporate group structure of the underlying social network, we use a generalized version of the configuration model in which each node is a member of a specified number of triangles. SIR epidemics on this type of graph have earlier been investigated under the assumption of homogeneous infectivity and also under the assumption of Poisson transmission and recovery rates. We extend known results from literature by relaxing the assumption of homogeneous infectivity both in individual infectivity and between different kinds of neighbours. An important special case of the epidemic model analysed in this paper is epidemics in continuous time with arbitrary infectious period distribution. We use branching process approximations of the spread of the disease to provide expressions for the basic reproduction number R_0, the probability of a major outbreak and the expected final size. In addition, the impact of random vaccination with a perfect vaccine on the final outcome of the epidemic is investigated. We find that, for this particular model, R_0 equals the perfect vaccine-associated reproduction number. Generalizations to groups larger than three are discussed briefly.

Zika Virus: A Surprising Savage Infection Worldwide

The outbreak of zika virus belonging to the flavivirus genus was first reported in 1947 in the monkey species in Uganda. Then it was first isolated from the Aedes mosquito’s species. Recent outbreaks have been reported in India also. The main host of the virus is humans like all other flaviviruses. Although the fatality rate is not so high but the effects are seen majorly on the fetus when pregnant women gets infected. No perfect treatment or vaccine has been developed yet to treat the disease. In India also few cases are now being reported and it shows that the outbreak of the virus is just not limited to Brazil and America but now also to Asian countries as well and gradually worldwide its infection will spread through. This article deals with the development of the zika virus from 1947 to 2018 and the preventive measures in order to prevent future outbreaks have been considered.

Three-strategy and four-strategy model of vaccination game introducing an intermediate protecting measure

We build a new analytic scheme that competently reproduces the decision-making process of choosing an imperfect provision based on the evolutionary game theory dovetailed with the SIR model for epidemic spreading dynamics. Aside from considering the two extreme options whether or not taking vaccination, we consider an ‘intermediate defense measure’ (IDM) that emulates hand-washing, masking, gargling, and taking energy drinks, defined as the third strategy while taking vaccination as well as IDM at the same time as the fourth strategy. In the present study, each of the proposed three imperfect provisions is able to oppress infectious diseases like Flu, Influenza, Ebola, and SARS during an epidemic season with certain extent. Considering an infinite and well-mixed population, a new analytic framework is built to take care of those three cases instead of perfect vaccination. Unlike MAS (multi-agent simulation) approach we conduct our study throughout using the so-called theoretical approach. Besides that, three different strategy updating rules based on evolutionary game theory have also been considered in our proposed model. We successfully obtain phase diagrams showing the final epidemic size, social average payoff and the respective fractions of the different strategy holders using various values of effectiveness and efficiency coefficients. Finally, a comprehensive discussion is made with comparison among the two-, three- and four- strategy models to get a holistic idea justifying how imperfect provisions work during an epidemic spreading.

Identifying a sufficient core group for trachoma transmission.

BackgroundIn many infectious diseases, a core group of individuals plays a disproportionate role in transmission. If these individuals were effectively prevented from transmitting infection, for example with a perfect vaccine, then the disease would disappear in the remainder of the community. No vaccine has yet proven effective against the ocular strains of chlamydia that cause trachoma. However, repeated treatment with oral azithromycin may be able to prevent individuals from effectively transmitting trachoma.Methodology/Principal findingsHere we assess several methods for identifying a core group for trachoma, assuming varying degrees of knowledge about the transmission process. We determine the minimal core group from a completely specified model, fitted to results from a large Ethiopian trial. We compare this benchmark to a core group that could actually be identified from information available to trachoma programs. For example, determined from the rate of return of infection in a community after mass treatments, or from the equilibrium prevalence of infection.Conclusions/SignificanceSufficient groups are relatively easy for programs to identify, but will likely be larger than the theoretical minimum.

The Vaccine and Its Simulacra: Agnotology, Ontology and Biopolitics in France, 1800–1865

Abstract The advent of smallpox vaccine in France in 1800 inaugurates a new relationship between administration, public health and the definition of medical facts. As Napoleon himself refused to establish compulsory vaccination, a Comité de vaccine was established so as to impose the idea of a riskless vaccine protecting forever from smallpox. This article studies how human experimentation, clinical experience, medical imagery and statistics maintained the idea of a perfect vaccine for six decades, despite the multiplication of cases of post-vaccination smallpox and vaccine contaminations.

Which is more effective for suppressing an infectious disease: imperfect vaccination or defense against contagion?

We consider two imperfect ways to protect against an infectious disease such as influenza, namely vaccination giving only partial immunity and a defense against contagion such as wearing a mask. We build up a new analytic framework considering those two cases instead of perfect vaccination, conventionally assumed as a premise, with the assumption of an infinite and well-mixed population. Our framework also considers three different strategy-updating rules based on evolutionary game theory: conventional pairwise comparison with one randomly selected agent, another concept of pairwise comparison referring to a social average, and direct alternative selection not depending on the usual copying concept. We successfully obtain a phase diagram in which vaccination coverage at equilibrium can be compared when assuming the model of either imperfect vaccination or a defense against contagion. The obtained phase diagram reveals that a defense against contagion is marginally inferior to an imperfect vaccination as long as the same coefficient value is used.Highlights– We build a new analytical framework for a vaccination game combined with the susceptible-infected-recovered (SIR) model.– Our model can evaluate imperfect provisions such as vaccination giving only partial immunity and a defense against contagion.– We obtain a phase diagram with which to compare the quantitative effects of partial vaccination and a defense against contagion.

Leishmaniasis in humans: drug or vaccine therapy?

Leishmania is an obligate intracellular pathogen that invades phagocytic host cells. Approximately 30 different species of Phlebotomine sand flies can transmit this parasite either anthroponotically or zoonotically through their bites. Leishmaniasis affects poor people living around the Mediterranean Basin, East Africa, the Americas, and Southeast Asia. Affected regions are often remote and unstable, with limited resources for treating this disease. Leishmaniasis has been reported as one of the most dangerous neglected tropical diseases, second only to malaria in parasitic causes of death. People can carry some species of Leishmania for long periods without becoming ill, and symptoms depend on the form of the disease. There are many drugs and candidate vaccines available to treat leishmaniasis. For instance, antiparasitic drugs, such as amphotericin B (AmBisome), are a treatment of choice for leishmaniasis depending on the type of the disease. Despite the availability of different treatment approaches to treat leishmaniasis, therapeutic tools are not adequate to eradicate this infection. In the meantime, drug therapy has been limited because of adverse side effects and unsuccessful vaccine preparation. However, it can immediately make infections inactive. According to other studies, vaccination cannot eradicate leishmaniasis. There is no perfect vaccine or suitable drug to eradicate leishmaniasis completely. So far, no vaccine or drug has been provided to induce long-term protection and ensure effective immunity against leishmaniasis. Therefore, it is necessary that intensive research should be performed in drug and vaccine fields to achieve certain results.

Summertime, and the livin’ is easy: Winter and summer pseudoseasonal life expectancy in the United States

In temperate climates, mortality is seasonal with a winter-dominant pattern, due in part to pneumonia and influenza. Cardiac causes, which are the leading cause of death in the United States, are also winter-seasonal although it is not clear why. Interactions between circulating respiratory viruses (f.e., influenza) and cardiac conditions have been suggested as a cause of winter-dominant mortality patterns. We propose and implement a way to estimate an upper bound on mortality attributable to winter-dominant viruses like influenza. We calculate 'pseudo-seasonal' life expectancy, dividing the year into two six-month spans, one encompassing winter the other summer. During the summer when the circulation of respiratory viruses is drastically reduced, life expectancy is about one year longer. We also quantify the seasonal mortality difference in terms of seasonal "equivalent ages" (defined herein) and proportional hazards. We suggest that even if viruses cause excess winter cardiac mortality, the population-level mortality reduction of a perfect influenza vaccine would be much more modest than is often recognized.

A model to assess the effect of vaccine compliance on Human Papillomavirus infection and cervical cancer

• A two-sex deterministic model for the transmission dynamics of HPV is developed. • Younger females are assumed more sensitive to infection and subject to vaccination. • Older females are assumed at a higher risk of developing cervical cancer. • Vaccine compliance is the key to eradicating HPV and cervical cancer. • Male vaccination has significant benefit to females. Three doses of a Human Papillomavirus (HPV) vaccine are recommended for both males and females, and compliance is a major challenge. In this paper a deterministic model for HPV infection and cervical cancer is constructed and rigorously analyzed for the effects of vaccine compliance. The model is based on ordinary differential equations and incorporates cohort vaccination of males and females before entering the sexually-active class as well as a fraction that starts taking the vaccine after entering the sexually-active class. The female population is further stratified into two age groups. The first group is at a higher risk for new HPV infection, is not likely to develop cervical cancer, and is subject to three doses of an HPV vaccine. The second age group has reduced chances of acquiring new infections but is at a higher risk for developing cervical cancer resulting from a persistent HPV infection. No fresh HPV vaccine is administered in this age group. The model has a locally asymptotically-stable disease-free equilibrium but may also admit endemic equilibria when the epidemic threshold, namely the effective reproduction number, R v , is below unity. Using the center manifold theory it is shown that the model exhibits a backward bifurcation at R v = 1 , which is caused due to the imperfect HPV vaccine. For the case of a perfect vaccine, the disease-free equilibrium is proved to be globally asymptotically-stable, under certain additional conditions, when R v ≤ 1 . Multiple endemic equilibria may exist when R v > 1 . It is shown through numerical simulations that vaccine compliance (with all three doses) is necessary for the reduction of HPV infections and cervical cancer. Lack of compliance may lead to a higher number of infections and cancer cases in the long run.

Persistence and stability of the disease-free equilibrium in a stochastic epidemic model with imperfect vaccine

This paper concerns the dynamics of a stochastic SIVR epidemic model with imperfect vaccine where, differently from the epidemic model with perfect vaccine, the vaccinated is perturbed by the noise. This difference is the main difficulty to be conquered to give the threshold $R_{0}^{S}$ . Firstly, $R_{0}^{S}>1$ is proved to be sufficient for persistence in mean of the system. Then, three conditions for the disease to die out are given, which improve the previously known results on extinction of the disease. In case that the disease goes extinct, we show that the disease-free equilibrium is almost surely stable by using the nonnegative semimartingale convergence theorem.

Vector-based genetically modified vaccines: Exploiting Jenner’s legacy

The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of ’smarter’ vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. It may be speculated that novel GM technologies will significantly contribute to their development. While a promising number of studies is conducted on GM vaccines and GM vaccine technologies, the contribution of GM technology to newly introduced vaccines on the market is disappointingly limited.In this study, the field of vector-based GM vaccines is explored. Data on currently available, actually applied, and newly developed vectors is retrieved from various sources, synthesised and analysed, in order to provide an overview on the use of vector-based technology in the field of GM vaccine development. While still there are only two vector-based vaccines on the human vaccine market, there is ample activity in the fields of patenting, preclinical research, and different stages of clinical research. Results of this study revealed that vector-based vaccines comprise a significant part of all GM vaccines in the pipeline. This study further highlights that poxviruses and adenoviruses are among the most prominent vectors in GM vaccine development.After the approval of the first vectored human vaccine, based on a flavivirus vector, vaccine vector technology, especially based on poxviruses and adenoviruses, holds great promise for future vaccine development. It may lead to cheaper methods for the production of safe vaccines against diseases for which no or less perfect vaccines exist today, thus catering for an unmet medical need. After the introduction of Jenner’s vaccinia virus as the first vaccine more than two centuries ago, which eventually led to the recent eradication of smallpox, this and other viruses may now be the basis for constructing vectors that may help us control other major scourges of mankind.

Genetic and antigenic characterization of hemagglutinin of influenza A/H3N2 virus from the 2015 season in Thailand.

Antigenic changes in the HA1 domain of the influenza A/H3N2 hemagglutinin (HA) present a challenge in the design of the annual influenza vaccine. We examined the genetic variability in the nucleotide and amino acid of encoding HA1 sequences of the influenza A/H3N2 virus during the 2015 influenza season in Thailand. Toward this, the HA genes of 45 influenza A/H3N2 strains were amplified and sequenced. Although a clade 3C.3a strain (A/Switzerland/9715293/2013) was chosen for the 2015 vaccine, phylogenetic analysis demonstrated that strains belonging to clade 3C.2a (96%) instead of clade 3C.3a (4%) were circulating that year. Sequence analysis showed that seven codons were under positive selection, five of which were located inside the antigenic epitopes. The percentages of the perfect match vaccine efficacy (VE) estimated by the P epitope model against circulating strains suggested antigenic drift of the dominant epitopes A and B, which contributed to reduced VE of the 2015 vaccine. However, the 2016 vaccine strain (A/Hong Kong/4801/2014) was closely related and well matched against the circulating strain (mean of VE=79.3%). These findings provide data on the antigenic drift of the influenza A/H3N2 virus circulating in Thailand and further support continual monitoring and surveillance of the antigenic changes on HA1.

A recombinant rabies virus carrying GFP between N and P affects viral transcription in vitro.

Several studies have demonstrated the rabies virus to be a perfect potential vaccine vector to insert foreign genes into the target genome. For this study, a green fluorescent protein (GFP) gene was cloned into the rabies virus (RABV) genome between the N and P gene. CT dinucleotide was inserted as intergenic region. The recombinant high egg passage Flury strain (HEP-Flury) of RABV, carrying GFP (rHEP-NP-GFP), was generated in BHK-21 cells using reverse genetics. According to the viral growth kinetics assay, the addition of GFP between N and P gene has little effect on the viral growth compared to the parental strain HEP-Flury. Quantitative real-time PCR (qPCR) indicated that rHEP-NP-GFP showed different viral gene transcription, especially for G gene, compared to HEP-Flury. The same is true for one other recombinant RABV carrying GFP between G and L gene in NA cells. In addition, parent HEP-Flury showed more expression of innate immune-related molecules in NA cells. Compared to HEP-Flury, Western blotting (WB) indicated that insertion of a foreign gene following N gene enhanced the expression of M and G proteins. According to the qPCR and WB, GFP expression levels of rHEP-NP-GFP were significantly higher than rHEP-GFP. This study indicates HEP-Flury as valid vector to express exogenous genes between N and P.

Reproduction numbers for epidemic models with households and other social structures II: Comparisons and implications for vaccination

In this paper we consider epidemic models of directly transmissible SIR (susceptible → infective → recovered) and SEIR (with an additional latent class) infections in fully-susceptible populations with a social structure, consisting either of households or of households and workplaces. We review most reproduction numbers defined in the literature for these models, including the basic reproduction number R0 introduced in the companion paper of this, for which we provide a simpler, more elegant derivation. Extending previous work, we provide a complete overview of the inequalities among these reproduction numbers and resolve some open questions. Special focus is put on the exponential-growth-associated reproduction number Rr, which is loosely defined as the estimate of R0 based on the observed exponential growth of an emerging epidemic obtained when the social structure is ignored. We show that for the vast majority of the models considered in the literature Rr ≥ R0 when R0 ≥ 1 and Rr ≤ R0 when R0 ≤ 1. We show that, in contrast to models without social structure, vaccination of a fraction 1−1/R0 of the population, chosen uniformly at random, with a perfect vaccine is usually insufficient to prevent large epidemics. In addition, we provide significantly sharper bounds than the existing ones for bracketing the critical vaccination coverage between two analytically tractable quantities, which we illustrate by means of extensive numerical examples.

A Model of Perfect Pediatric Vaccination of Dengue with Delay and Optimal Control

A delayed mathematical model of Dengue dynamical transmission between vector mosquitoes and human, incorporating a control strategy of perfect pediatric vaccination is proposed in this paper. By some analytical skills, we obtain the existence of disease-free equilibria and endemic equilibrium, the necessary conditions of global asymptotical stability about two disease-free equilibria. Further, by Pontryagin’s maximum principle, we obtain the optimal control of the disease. Finally, numerical simulations are carried out to verify the correctness of the theoretical results and feasibility of the control measure.

European regions and the territorial integrity of european states: Galicia-Spain-Europe as a model of cohesion and integration

The EU is a union of democratic States and, therefore, it respects individual and collective rights. It is a unique organization because it exquisitely respects the rights of minorities and because it does not aspire to unify neither homogenize the different cultures which coexist in Europe. Fortunately, we, Europeans have learnt this hard and bitter lesson from our history. The times of invasions and wars of religion are already over; therefore, the perfect vaccine against our old mistakes is the respect for the diversity inside Europe.

Simulating sterilization, vaccination, and test-and-remove as brucellosis control measures in bison

Brucella abortus, the causative agent of bovine brucellosis, infects wildlife, cattle, and humans worldwide, but management of the disease is often hindered by the logistics of controlling its prevalence in wildlife reservoirs. We used an individually based epidemiological model to assess the relative efficacies of three management interventions (sterilization, vaccination, and test-and-remove). The model was parameterized with demographic and epidemiological data from bison in Yellowstone National Park, USA. Sterilization and test-and-remove were most successful at reducing seroprevalence when they were targeted at young seropositive animals, which are the most likely age and sex category to be infectious. However, these approaches also required the most effort to implement. Vaccination was less effective (even with a perfect vaccine) but also required less effort to implement. For the treatment efforts we explored (50-100 individuals per year or 2.5-5% of the female population), sterilization had little impact upon the bison population growth rate when selectively applied. The population growth rate usually increased by year 25 due to the reduced number of Brucella-induced abortions. Initial declines in seroprevalence followed by rapid increases (.15% increase in 5 years) occurred in 3-13% of simulations with sterilization and test-and-remove, but not vaccination. We believe this is due to the interaction of superspreading events and the loss of herd immunity in the later stages of control efforts as disease prevalence declines. Sterilization provided a mechanism for achieving large disease reductions while simultaneously limiting population growth, which may be advantageous in some management scenarios. However, the field effort required to find the small segment of the population that is infectious rather than susceptible or recovered will likely limit the utility of this approach in many free-ranging wildlife populations. Nevertheless, we encourage scientists and policy makers to consider sterilization as part of a suite of available brucellosis management tools.

An age-structured model of human papillomavirus vaccination

Recently, a vaccine for human papillomavirus was introduced, but made available only for girls and adult women aged 13–26. Since rates of sexual activity vary by age and gender, vaccinating only an age-limited subset of one cohort may be insufficient to control the disease across all age groups and genders. We develop an age-dependent two-sex mathematical model to describe the HPV vaccination program for a vaccine targeting HPV types 16 and 18 in both childhood and adult stages. A stability analysis is performed to determine the stability of the disease-free and endemic equilibria for different vaccination programs. The basic reproduction number is derived for perfect childhood vaccination, perfect adult vaccination and childhood–adult vaccination. We show that the effects of age dependency are complex, but that vaccinating a single age cohort in one gender, as current programs do, can result in eventual control of the disease across all age groups. We also support our theoretical analysis with numerical simulations. This provides a framework for future research and public-health policy to determine the dependence of HPV vaccination programs on age and sexual behaviour, as well as how the vaccine can reduce the number of infections and deaths due to cervical cancer.