Perfect Vaccine Research Articles

Seasonal spread and control of Bluetongue in cattle

Bluetongue is a seasonal midge-borne disease of ruminants with economic consequences on herd productivity and animal trade. Recently, two new modes of transmission have been demonstrated in cattle for Bluetongue virus serotype 8 (BTV8): vertical and pseudo-vertical transmission. Our objective was to model the seasonal spread of BTV8 over several years in a homogeneous population of cattle, and to evaluate the effectiveness of vaccination strategies. We built a deterministic mathematical model accounting for the seasonality in vector abundance and all the modes of transmission. We proposed a counterpart of the basic reproduction number ( R 0) in a seasonal context ( R S ). Set A( t) is the number of secondary cases produced by a primary case introduced at time t. R S is the average of A( t). It is a function of midge abundance and vaccination strategy. We also used A ⁎, the maximum of A( t), as an indicator of the risk of an epidemic. Without vaccination, the model predicted a large first epidemic peak followed by smaller annual peaks if R S >1. When R S <1, small epidemics could occur if A ⁎ >1. Vaccination reduced R S and A ⁎ to less than one, but almost perfect vaccine efficacy and coverage were required to ensure no epidemics occurred. However, a lower coverage resulting in R S>1 could decrease infection prevalence. A further step would be to optimize vaccination strategies by targeting an appropriate period of the year to implement the vaccination.

Genetic Structure of Human A/H1N1 and A/H3N2 Influenza Virus on Corsica Island: Phylogenetic Analysis and Vaccine Strain Match, 2006–2010

BackgroundThe aim of this study was to analyse the genetic patterns of Hemagglutinin (HA) genes of influenza A strains circulating on Corsica Island during the 2006–2009 epidemic seasons and the 2009–2010 pandemic season.MethodsNasopharyngeal samples from 371 patients with influenza-like illness (ILI) were collected by General Practitioners (GPs) of the Sentinelles Network through a randomised selection routine.ResultsPhylogenetic analysis of HA revealed that A/H3N2 strains circulating on Corsica were closely related to the WHO recommended vaccine strains in each analyzed season (2006–2007 to 2008–2009). Seasonal Corsican influenza A/H1N1 isolated during the 2007–2008 season had drifted towards the A/Brisbane/59/2007 lineage, the A/H1N1 vaccine strain for the 2008–2009 season. The A/H1N1 2009 (A/H1N1pdm) strains isolated on Corsica Island were characterized by the S220T mutation specific to clade 7 isolates. It should be noted that Corsican isolates formed a separate sub-clade of clade 7 as a consequence of the presence of the fixed substitution D222E.The percentages of the perfect match vaccine efficacy, estimated by using the p epitope model, against influenza viruses circulating on Corsica Island varied substantially across the four seasons analyzed, and tend to be highest for A/H1N1 compared with A/H3N2 vaccines, suggesting that cross-immunity seems to be stronger for the H1 HA gene.ConclusionThe molecular analysis of the HA gene of influenza viruses that circulated on Corsica Island between 2006–2010 showed for each season the presence of a dominant lineage characterized by at least one fixed mutation. The A/H3N2 and A/H1N1pdm isolates were characterized by multiples fixation at antigenic sites. The fixation of specific mutations at each outbreak could be explained by the combination of a neutral phenomenon and a founder effect, favoring the presence of a dominant lineage in a closed environment such as Corsica Island.

Immunoprophylaxis of bovine respiratory syndrome

Bovine Respiratory Syndrome (BRS) is a multifactorial disease caused by the interaction of infective agents, the environment and the individual immunological response of animals in the herd. Despite five decades of research on BRS, no clear understanding of how environmental factors influence pathogenic outcomes of the disease has been defined. As such, the development of immunoprophylaxis and vaccine programmes to prevent outbreaks of BRS in cattle has not been successful. The current paper discusses vaccination programmes for all categories of cattle and presents a review of existing vaccines being used for immunoprophylaxis of respiratory syndrome in cattle and discusses the advantages and disadvantages of the currently used vaccines and vaccination programmes. Lastly, a discussion detailing the design of future perfect vaccines is presented.

Reproductive numbers, epidemic spread and control in a community of households

Many of the studies on emerging epidemics (such as SARS and pandemic flu) use mass action models to estimate reproductive numbers and the needed control measures. In reality, transmission patterns are more complex due to the presence of various social networks. One level of complexity can be accommodated by considering a community of households. Our study of transmission dynamics in a community of households emphasizes five types of reproductive numbers for the epidemic spread: household-to-household reproductive number, leaky vaccine-associated reproductive numbers, perfect vaccine reproductive number, growth rate reproductive number, and the individual reproductive number. Each of those carries different information about the transmission dynamics and the required control measures, and often some of those can be estimated from the data while others cannot. Simulations have shown that under certain scenarios there is an ordering for those reproductive numbers. We have proven a number of ordering inequalities under general assumptions about the individual infectiousness profiles. Those inequalities allow, for instance, to estimate the needed vaccine coverage and other control measures without knowing the various transmission parameters in the models. Along the way, we have also shown that in choosing between increasing vaccine efficacy and increasing coverage levels by the same factor, preference should go to efficacy.

SEROTYPE REPLACEMENT OF VERTICALLY TRANSMITTED DISEASES THROUGH PERFECT VACCINATION

Strain replacement occurs when after a vaccination campaign one (or more) strains decline in prevalence while another strain (or strains) rise in prevalence. Differential effectiveness of the vaccine is the widely accepted and the most important mechanism which leads to this replacement effect. Recent theoretical studies have suggested that strain replacement may occur even if the vaccine is perfect, that is, the vaccine is completely effective with respect to all strains present. It has already been shown that perfect vaccination, along with a trade-off mechanism, such as co-infection or super-infection, lead to strain replacement. In this paper, we examine the hypothesis that strain replacement with perfect vaccination occurs only with trade-off mechanisms which allow a strain with a lower reproduction number to eliminate a strain with a higher reproduction number in the absence of vaccination. We test this hypothesis on a two-strain model with vertical transmission. We first show that vertical transmission as a trade-off mechanism can lead to dominance of a strain with suboptimal reproduction number. Based on the hypothesis we expect, and we show, that strain replacement occurs with vertical transmission.

Vaccines against Human Papillomaviruses - A Major Breakthrough in Cancer Prevention

Carcinoma of the cervix (CaCer) is the second most frequent malignancy in women on a global scale. Epidemiological studies carried out at the beginning of the second half of the 20th century showed that CaCer was of infectious nature and that its agent was transmitted by sexual intercourse. For some 15 years, herpes simplex virus type 2 (HSV2), the genital herpes virus, was suspected to be the etiological agent. This hypothesis was disproved just in the time when the first convincing evidence that the agents of the disease were human papillomaviruses (HPVs) was produced. Copious new findings obtained during the 1980's and 1990's unequivocally confirmed that HPVs were the causative agents. The most dangerous among the over 100 HPV types are types 16 and 18, which together account for over 70% of CaCer cases and very likely also for most of the other malignancies of the anogenital region and the oropharynx. Extensive research of the HPV biology and immunology enabled the development of vaccines based on the s.c. virus-like particles (VLP) prepared by genetic engineering. At present, there is one HPV vaccine on the market; it contains, besides types 16 and 18, also types 6 and 11, the causative agents of certain benign tumours of the genital area and of the larynx. A new vaccine, comprising types 16 and 18 only, the product of another firm, is to appear on the market soon. Both vaccines have already been tested in extensive clinical trials. They are nearly 100% effective, only very weakly reactogenic and they undoubtedly belong among the most perfect vaccines ever produced. The darker side of the anti-HPV vaccines is their high price, the fact that the highest benefits they bring will only become evident in 20 or 30 years, and that they do not afford protection against all oncogenic HPVs. It is therefore imperative that organized cytological screening be continued: it is destined to remain the main instrument of CaCer prevention for several decades. With all probability also other types of vaccine are under development, viz. VLP-based vaccines, whose range of applicability will be wider than that of the present preventive vaccines, as well as vaccines that will, hopefully, be able to inhibit already progressing infection or will be utilizable in CaCer immunotherapy.

Income and Health in Cities: the Messages from Stylized Facts

The benefits of good health to individuals and to society are strongly positive, and improving the health of the poor is a key millennium development goal (MDG). A typical health strategy advocated by some calls for increased public spending on health targeted to favor the poor backed by foreign assistance, combined with an international effort to perfect drugs and vaccines to ameliorate the major infectious diseases prevalent in developing nations. However, if the objective is better health outcomes at the least cost and a reduction in urban health inequity, our research suggests that the four most potent policy interventions are: improving access to clean water and sanitation; widely available primary care and health programs aimed at influencing diets and lifestyles; raising the level of education; and better urban land use and transport planning which contains urban sprawl and minimizes the trend towards sedentary living habits. The payoff from these four, in terms of health outcomes especially for those in low-income categories, dwarfs the returns from new drugs and curative hospital-based medicine, although these certainly have their place in a modern urban health system. We find, moreover, that the resource requirements for successful health care policies are likely to depend on an acceleration of economic growth rates, which increase household purchasing power and enlarge the pool of resources available to national and subnational governments to invest in and maintain health-related infrastructure and services. Thus, an acceleration of growth rates may be necessary to sustain a viable urban health strategy, which is equitable, and to ensure steady gains in health outcomes.

Strain replacement in an epidemic model with super-infection and perfect vaccination

Several articles in the recent literature discuss the complexities of the impact of vaccination on competing subtypes of one micro-organism. Both with competing virus strains and competing serotypes of bacteria, it has been established that vaccination has the potential to switch the competitive advantage from one of the pathogen subtypes to the other resulting in pathogen replacement. The main mechanism behind this process of substitution is thought to be the differential effectiveness of the vaccine with respect to the two competing micro-organisms. In this article, we show that, if the disease dynamics is regulated by super-infection, strain substitution may indeed occur even with perfect vaccination. In fact we discuss a two-strain epidemic model in which the first strain can infect individuals already infected by the second and, as far as vaccination is concerned, we consider a best-case scenario in which the vaccine provides perfect protection against both strains. We find out that if the reproduction number of the first strain is smaller than the reproduction number of the second strain and the first strain dominates in the absence of vaccination then increasing vaccination levels promotes coexistence which allows the first strain to persist in the population even if its vaccine-dependent reproduction number is below one. Further increase of vaccination levels induces the domination of the second strain in the population. Thus the second strain replaces the first strain. Large enough vaccination levels lead to the eradication of the disease.

Understanding dengue pathogenesis: implications for vaccine design.

In the second half of the twentieth century dengue spread throughout the tropics, threatening the health of a third of the world's population. Dengue viruses cause 50-100 million cases of acute febrile disease every year, including more than 500,000 reported cases of the severe forms of the disease--dengue haemorrhagic fever and dengue shock syndrome. Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. The current understanding of dengue pathogenesis is outlined in this review, with special emphasis on the role of the immune response. The suspected involvement of the immune system in increased disease severity and vascular damage has raised concerns about every vaccine design strategy proposed so far. Clearly more research is needed on understanding the correlates of protection and mechanisms of pathogenesis. There is, however, an urgent need to provide a solution to the escalating global public health problems caused by dengue infections. Better disease management, vector control and improved public health measures will help reduce the current disease burden, but a safe and effective vaccine is probably the only long-term solution. Although concerns have been raised about the possible safety and efficacy of both conventional and novel vaccine technologies, the situation is now so acute that it is not possible to wait for the perfect vaccine. Consequently the careful and thorough evaluation of several of the current candidate vaccines may be the best approach to halting the spread of disease.

Vaccine delivery to animals

For many years vaccination of animals has been practiced to prevent infectious diseases using inactivated organisms or modified live organisms. The live vaccines were effective but lacked safety. The vaccines made with inactivated organisms required an adjuvant to induce an immune response that was not as effective as either the clinical disease or live vaccines. An ‘ideal’ vaccine would induce effective immunity specific for the type of infection, have long duration, require minimal or no boosters, have impeccable safety, would not induce adverse reactions, and be easy to administer. The desire to meet these criteria, and especially safety, has resulted in the development of vaccines that do not depend on the use of the viable disease agent. The emphasis on subunit or inactivated vaccines that meet the desired criteria of a perfect vaccine has resulted in a critical need for better adjuvants and delivery systems. This has resulted in a technological innovation revolution with development of a wide array of different technologies to generate effective vaccines. This review will describe the historical relevance of adjuvants used for parenterally administered inactivated/subunit vaccines as well as describe some of the exciting technological advances including adjuvants (ISCOMS), delivery systems (recombinant vectors, microparticles), and novel approaches (transgenic plants, naked DNA) that are currently being, or will be used in the future, in the search for better, more effective vaccines that meet the current and future needs of veterinary medicine.

IMMUNOTHERAPEUTIC STRATEGIES FOR CERVICAL SQUAMOUS CARCINOMA

Progress in developing preventive and therapeutic vaccines for HPV-associated diseases has been made in the last few years, but continued studies are needed to evaluate the clinical feasibility of different vaccination approaches and to determine a clinically effective and safe one. The perfect HPV vaccine will have both preventive and therapeutic capabilities, and because it is likely to be used world-wide, especially in developing countries, it must also have low production costs.

Imperfect vaccines and herd immunity to HIV.

A number of prophylactic vaccines against human immunodeficiency virus (HIV) have passed through phase I clinical trials, and phase II clinical trials are now being planned. These vaccines are not expected to be perfect and might fail in a number of different ways. This paper shows how to equate different aspects of imperfection in a prophylactic vaccine in terms of impact upon levels of herd immunity, and hence upon the vaccine coverage required for eradication. Such comparisons reveal that an otherwise perfect vaccine that gives protection which wanes with a half-life of 10 years is only as good as a vaccine that works in 30% of people giving them complete, lifelong protection. The paper goes on to compare predicted patterns of seroconversion that would be observed in clinical trials and in community-wide vaccination campaigns for vaccines that confer the same levels of herd immunity but are imperfect in different ways.

AIDS Vaccine Meeting: International Trials Soon

400 AIDS (acquired immunodeficiency syndrome) vaccine researchers and policy-makers met 15-19 October 1991 in Marco Island Florida to discuss plans for clinical trials of AIDS vaccines. 3 major health research institutions plan to begin testing vaccines: World Health Organization in Rwanda Uganda Brazil and Thailand; the U.S. Armys medical research division in Thailand and the Division of AIDS (DAIDS) of the U.S. National Institute of Allergy and Infectious Disease (NIAID in Zaire. 9 vaccines have already been tried in Phase I clinical trials for safety and an immune response. Conferees realize that plans for trials should be accelerated because HIV is spreading rapidly but also vaccine experiments are proving more promising than anticipated. A whole killed simian immunodeficiency virus vaccine and several genetically engineered HIV fragments have given hopeful results in primate experiments. Planners also realize that it will take until 1995 at least before any results of actual clinical trials will be available. The existing rate of spread of seropositivity in the test areas must be documented vaccines selected based on the endemic HIV strains in the area pilot trials must be mounted then actual trials completed. The consensus is that existing vaccines should be tested now while research on more perfect vaccines progresses.

What are the Risks of Risky Sex? Modeling the AIDS Epidemic

This paper employs mathematical models to examine the epidemic of AIDS among gay men. The approach allows consideration of arbitrary probability distributions for risky sex rates, the duration of sex lives, and the incubation time of AIDS following HIV infection, thus quite general models can be constructed. The analysis suggests what must happen for the epidemic to subside (barring a cure) by generalizing known formulas for the reproductive rate of HIV infection. This result shows that the simplifying assumption of exponential sex lives found in most other AIDS models is pessimistic relative to more realistic sex life distributions. It is also shown that under the assumption of random partner selection, the likelihood that a selected partner is infected exceeds the fraction of the population that is infected. Several scenarios illustrating the timeframe necessary for changes to occur in the AIDS case rate and the prevalence of HIV infection are presented. These scenarios are driven by assumptions regarding reduction in risky sex rates, or by the development of an imperfect immunizing vaccine, and are parameterized via data from recent AIDS cohort studies. Even under optimistic scenarios (such as abstinence from risky sex or the administration of a perfect vaccine), the model predicts that it would take over 15 years to eradicate AIDS in gay communities such as San Francisco where HIV prevalence is currently near 50%. Less optimistic scenarios force the conclusion that such communities will be living with AIDS for decades to come.

Points: The perfect rabies vaccine

Points: The perfect rabies vaccine

Pertussis Disease, Vaccine, and Controversy

Whooping cough affected as many as 265,000 persons and killed 9,000 to 12,000 at its peak in the United States in the 1930s. 1 Today, five to 20 persons die each year and the disease has been reduced to 1,000 to 2,000 cases per year. Pertussis vaccine was widely introduced in the 1950s and 1960s, and we have achieved a 90%+ rate of immunization among school-children. 2 It is not a perfect vaccine; some persons are only partially protected and some not at all. Furthermore, it has a high frequency of transient, nondamaging side effects, a lesser frequency of potentially serious adverse effects, and a remote risk of permanent neurological sequelae or death. 3 Given this brief summary, one might expect cautious rejoicing. We can rejoice in that, once again, preventive measures seem to have triumphed in diminishing disease; indeed, the reduction in pertussis is striking and impressive. We are

Asian influenza; clinical picture.

Of the great plagues that in past centuries regularly decimated the world population, only influenza remains. The recent pandemic of Asian influenza made very manifest the limits of our progress in the conquest of this scourge. Currently we know and can study the causative agent, have a good but far from perfect vaccine, and can treat most complications successfully. Incomplete is our knowledge concerning the clinical symptoms associated with influenzal infection, the variations in number and intensity of these symptoms, and their complications and sequelae. For these reasons it is appropriate to present and to record the complete clinical picture, observed in the New Orleans area during August, September, and October, 1957, in 76 patients who suffered from influenza, established by specific diagnostic tests to be due to influenza Type A, Asian strain. Background This study, one of many planned and initiated by the threat of an impending invasion of