Prospects for controlling future pandemics of influenza

Pandemic influenza remains one of the most serious threats to global public health and continued global vigilance to monitor emerging threats is crucial. Of the weapons available to control a pandemic, vaccination is potentially the most powerful, but there are currently serious limitations to timely availability of vaccine supply in an emergency. Many novel influenza vaccines are in development, some of which have the potential to deliver the massive quantities of vaccine that would be required in a pandemic in a short period of time. However, for the foreseeable future, it is likely that the principal vaccine that will be deployed in a pandemic will be an inactivated egg-derived vaccine of the kind that has been available for several decades. This review will focus on the practical hurdles that need to be surmounted to deliver large amounts of safe and effective pandemic vaccine to the general public. There needs to be a continued focus on improvement to the vaccine response system that will require close collaboration between influenza and vaccine experts, manufacturers, regulators and public health authorities around the world.     

Interspecies transmission of influenza A viruses and influenza pandemics

Molecular and genetic data are summarized on the origin of influenza A virus pandemic variants. Conceptual modifications of the reassortment theory of the origin of pandemic strains are discussed in connection with the appearance of new H5 and H9 avian influenza viruses, which caused the respiratory infection in man and which are presently in the focus of attention as possible agents of future pandemic.     

Malaria vaccines: high-throughput tools for antigens discovery with potential for their development

Malaria is a disease induced by parasites of the Plasmodium genus, which are transmitted by Anopheles mosquitoes and represents a great socio-economic burden Worldwide. Plasmodium vivax is the second species of malaria Worldwide, but it is the most prevalent in Latin America and other regions of the planet. It is currently considered that vaccines represent a cost-effective strategy for controlling transmissible diseases and could complement other malaria control measures; however, the chemical and immunological complexity of the parasite has hindered development of effective vaccines. Recent availability of several genomes of Plasmodium species, as well as bioinformatic tools are allowing the selection of large numbers of proteins and analysis of their immune potential. Herein, we review recently developed strategies for discovery of novel antigens with potential for malaria vaccine development.     

New technologies for influenza vaccines

Influenza vaccine preparations have been administered to humans since the late 1930s, and the diversity of approaches in licensed trivalent seasonal or monovalent pandemic products is unparalleled by vaccines against any other target. These approaches include inactivated whole virus vaccines, detergent or solvent "split" vaccines, subunit vaccines, live attenuated vaccines, adjuvanted vaccines, intramuscular vaccines, intradermal vaccines, intranasal vaccines, egg-produced vaccines and mammalian cell culture-produced vaccines. The challenges of influenza immunization, including multiple co-circulating strains, antigenic change over time, a broad age spectrum of disease, and the threat of pandemics, continue to drive the development of new approaches. This review describes some of the new approaches to influenza immunization that are the subjects of active research and development.     

The rationale for quadrivalent influenza vaccines

Two antigenically distinct lineages of influenza B viruses have circulated globally since 1985. However, licensed trivalent seasonal influenza vaccines contain antigens from only a single influenza B virus and thus provide limited immunity against circulating influenza B strains of the lineage not present in the vaccine. In recent years, predictions about which B lineage will predominate in an upcoming influenza season have been no better than chance alone, correct in only 5 of the 10 seasons from 2001 to 2011. Consequently, seasonal influenza vaccines could be improved by inclusion of influenza B strains of both lineages. The resulting quadrivalent influenza vaccines would allow influenza vaccination campaigns to respond more effectively to current global influenza epidemiology. Manufacturing capacity for seasonal influenza vaccines has increased sufficiently to supply quadrivalent influenza vaccines, and methods to identify the influenza B strains to include in such vaccines are in place. Multiple manufacturers have initiated clinical studies of quadrivalent influenza vaccines. Data from those studies, taken together with epidemiologic data regarding the burden of disease caused by influenza B infections, will determine the safety, effectiveness, and benefit of utilizing quadrivalent vaccines for the prevention of seasonal influenza disease.     

A 'small-world-like' model for comparing interventions aimed at preventing and controlling influenza pandemics

Background

The presence of the apolipoprotein E (APOE) ε4 allele is a major risk factor for the development of Alzheimer's disease (AD), and has been associated with metabolic brain changes several years before the onset of typical AD symptoms. Functional MRI (fMRI) is a brain imaging technique that has been used to demonstrate hippocampal activation during measurement of episodic encoding, but the effect of the ε4 allele on hippocampal activation has not been firmly established.

Methods

The present study examined the effects of APOE genotype on brain activation patterns in the medial temporal lobe (MTL) during an episodic encoding task using a well-characterized novel item versus familiar item contrast in cognitively normal, middle-aged (mean = 54 years) individuals who had at least one parent with AD.

Results

We found that ε3/4 heterozygotes displayed reduced activation in the hippocampus and MTL compared to ε3/3 homozygotes. There were no significant differences between the groups in age, education or neuropsychological functioning, suggesting that the altered brain activation seen in ε3/4 heterozygotes was not associated with impaired cognitive function. We also found that participants' ability to encode information on a neuropsychological measure of learning was associated with greater activation in the anterior MTL in the ε3/3 homozygotes, but not in the ε3/4 heterozygotes.

Conclusion

Together with previous studies reporting reduced glucose metabolism and AD-related neuropathology, this study provides convergent validity for the idea that the MTL exhibits functional decline associated with the APOE ε4 allele. Importantly, these changes were detected in the absence of meaningful neuropsychological differences between the groups. A focus of ongoing work in this laboratory is to determine if these findings are predictive of subsequent cognitive decline.     

Immune status of subjects inoculated with inactivated influenza vaccines

Inactivated whole-virion and split-virion influenza vaccines adsorbed on aluminium hydroxide did not suppress the immune system of the vaccinees. Immunization with these vaccine preparations induced the formation of both cell-mediated and humoral immunity in over 60% of the vaccinees.     

Prospects for the development of fungal vaccines.

In an era that emphasizes the term "cost-effective," vaccines are the ideal solution to preventing disease at a relatively low cost to society. Much of the previous emphasis has been on childhood scourges such as measles, mumps, rubella, poliomyelitis, and Haemophilus influenzae type b. The concept of vaccines for fungal diseases has had less impact because of the perceived limited problem. However, fungal diseases have become increasingly appreciated as serious medical problems that require recognition and aggressive management. The escalation in the incidence and prevalence of infection has prompted a renewed interest in vaccine development. Herein, I discuss the most recent developments in the search for vaccines to combat fungal infections. Investigators have discovered several inert substances from various fungi that can mediate protection in animal models. The next challenge will be to find the suitable mode of delivery for these immunogens.     

Universal influenza vaccines: developments, prospects for use

The review analyzes the developments of genetic engineering influenza vaccines based on the conservative epitopes of viral surface proteins, such as hemagglutinin, neuraminidase, ectodomain of matrix protein M2. It estimates the capacity of the vaccines to induce an immune response to a wide variety of influenza viruses, considers ways to increase the immunogenicity and protective properties of the vaccines, based on the conservative epitopes of viral surface proteins, and prospects for their use to prevent influenza.     

Human influenza vaccines and assessment of immunogenicity

Influenza is responsible for the infection of approximately 20% of the population every season and for an annual death toll of approximately half a million people. The most effective means for controlling infection and thereby reducing morbidity and mortality is vaccination by injection with an inactivated vaccine, or by intranasal administration of a live-attenuated vaccine. Protection is not always optimal and there is a need for the development of new vaccines with improved efficacy and for the expansion of enrollment into vaccination programs. An overview of old and new vaccines is presented. Methods of monitoring immune responses such as hemagglutination-inhibition, ELISA and neutralization tests are evaluated for their accuracy in the assessment of current and new-generation vaccines.     

Comparative analysis of six European influenza vaccines

Three split-virion vaccines (Vaxigrip, Begrivac, and Influsplit/Fluarix) and three subunit vaccines containing only viral surface glycoproteins (Influvac, Agrippai, and Fluvirin) available for the 1994–95 season were analysed by biological, molecular, and biochemical methods. Although all vaccines are required by health authorities to contain 15 g haemagglutinin per dose of each virus strain, there were significant differences in haemagglutination titres among the examined vaccines of both types. The enzymatic activity of neuraminidase was present in all vaccines except Fluvirin. Total protein content was lower for subunit vaccines. Viral nucleoprotein was detected in all split vaccines but to varying levels according to SDS-PAGE and Western blot analyses. The ovalbumin content was low in general but was about tenfold higher for Influvac than for the other vaccines analysed. This protein may induce hypersensitive reactions among persons with severe egg allergy. All three split-virion vaccines were found to contain the matrix protein; however, it was not detected in the subunit vaccines. Differences in influenza antigen variety in currently available vaccines may affect efficacy, whereas differences in concentrations of nonviral compounds such as ovalbumin and endotoxin may lead to different postvaccination reactogenicity profiles.     

Review of diphtheria, tetanus and pertussis vaccines in clinical development

Diphtheria, tetanus and pertussis vaccines have formed the cornerstone of childhood immunization programs for decades. Historically, these have comprised diphtheria and tetanus toxoids combined with inactivated whole-cell pertussis. More recently, advances have been made with the development of purified acellular pertussis vaccines, with improved reactogenicity profiles, and formulation with additional vaccines such as Haemophilus influenzae type b, hepatitis B virus and inactivated poliovirus. Development is currently focused on maximizing the number of vaccines that can be combined in a single formulation and strategies to provide protection against pertussis before the commencement of routine infant immunization.     

Gene constellation of live influenza A vaccines

Summary The genotypic composition of several H₃N₂ vaccinal strains made from PR/8/34 and different wild isolates has been determined. The results suggested that specific gene constellations at the level of the 3 largest RNA fragments, coding the 3 polymerase proteins are responsible for their consistent attenuation.Part of this study was supported by a grant from the Institut pour l'Encouragement de la Recherche Scientifique dans l'Industrie et l'Agriculture (I.R.S.I.A.).