Opportunities and challenges for T cell-based influenza vaccines.

Vaccination remains our main defence against influenza, which causes substantial annual mortality and poses a serious pandemic threat. Influenza virus evades immunity by rapidly changing its surface antigens but, even when the vaccine is well matched to the current circulating virus strains, influenza vaccines are not as effective as many other vaccines. Influenza vaccine development has traditionally focused on the induction of protective antibodies, but there is mounting evidence that T cell responses are also protective against influenza.

Development of vaccines at the time of COVID-19.

In December 2019, a working group of the European Academy of Microbiology assembled to discuss various aspects of vaccines and vaccinations. The meeting was organised by Jörg Hacker and Eliora Z. Ron and took place in the offices of the Leopoldina (German National Academy of Sciences Leopoldina).

Detection of enteroviruses in stools precedes islet autoimmunity by several months: possible evidence for slowly operating mechanisms in virus-induced autoimmunity.

Aims/hypothesis: This case-control study was nested in a prospective birth cohort to evaluate whether the presence of enteroviruses in stools was associated with the appearance of islet autoimmunity in the Type 1 Diabetes Prediction and Prevention study in Finland.

Methods: Altogether, 1673 longitudinal stool samples from 129 case children who turned positive for multiple islet autoantibodies and 3108 stool samples from 282 matched control children were screened for the presence of enterovirus RNA using RT-PCR. Viral genotype was detected by sequencing.

The role of the vaccines industry in Mission Grand Convergence.

The vast majority of vaccines used throughout the world are supplied by the private sector. It is essential therefore that the industry is closely engaged in future policy developments at a national and international level and is able to respond to the changing needs and priorities that may be required to ensure the success of Mission Grand Convergence. Uniquely, the major vaccine companies have the expertise and technical capacity to develop, produce and supply vaccines on a global scale.

CX3CR1 Is Expressed in Differentiated Human Ciliated Airway Cells and Co-Localizes with Respiratory Syncytial Virus on Cilia in a G Protein-Dependent Manner.

Respiratory syncytial virus (RSV) is the principal cause of bronchiolitis in infants and a significant healthcare problem. The RSV Glycoprotein (G) mediates attachment of the virus to the cell membrane, which facilitates interaction of the RSV Fusion (F) protein with nucleolin, thereby triggering fusion of the viral and cellular membranes. However, a host protein ligand for G has not yet been identified.

A preclinical study on the efficacy and safety of a new vaccine against Coxsackievirus B1 reveals no risk for accelerated diabetes development in mouse models.

Aims/hypothesis: Enterovirus infections have been implicated in the aetiology of autoimmune type 1 diabetes. A vaccine could be used to test the causal relationship between enterovirus infections and diabetes development. However, the development of a vaccine against a virus suspected to induce an autoimmune disease is challenging, since the vaccine itself might trigger autoimmunity.

Low doses of flagellin-L2 multimer vaccines protect against challenge with diverse papillomavirus genotypes.

Genetically modified bacterial flagellin (Fla), a Toll-like receptor-5 (TLR5) ligand, was evaluated as a fusion partner for human papillomavirus (HPV) L2-based immunogens in two animal challenge models; either cutaneous inoculation of rabbits with HPV 'quasivirions' containing cottontail rabbit papillomavirus (CRPV) genomes that induce warts, or intra-vaginal inoculation of mice with HPV 'pseudovirions' encapsidating a luciferase reporter plasmid and measurement of bioluminescence to determine infectivity. An Escherichia coli production system was developed for flagellin-L2 (Fla-L2) fusions containing either monomeric HPV-16 L2 a.a.

Cross-serotype immunity induced by immunization with a conserved rhinovirus capsid protein.

Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model.

Coxsackievirus B1 is associated with induction of β-cell autoimmunity that portends type 1 diabetes.

The rapidly increasing incidence of type 1 diabetes implies that environmental factors are involved in the pathogenesis. Enteroviruses are among the suspected environmental triggers of the disease, and the interest in exploring the possibilities to develop vaccines against these viruses has increased. Our objective was to identify enterovirus serotypes that could be involved in the initiation of the disease process by screening neutralizing antibodies against 41 different enterovirus types in a unique longitudinal sample series from a large prospective birth-cohort study.

Immunogenicity and efficacy of intramuscular replication-defective and subunit vaccines against herpes simplex virus type 2 in the mouse genital model.

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted virus that is highly prevalent worldwide, causing a range of symptoms that result in significant healthcare costs and human suffering. ACAM529 is a replication-defective vaccine candidate prepared by growing the previously described dl5-29 on a cell line appropriate for GMP manufacturing. This vaccine, when administered subcutaneously, was previously shown to protect mice from a lethal vaginal HSV-2 challenge and to afford better protection than adjuvanted glycoprotein D (gD) in guinea pigs.

Vaccine production, distribution, access, and uptake.

For human vaccines to be available on a global scale, complex production methods, meticulous quality control, and reliable distribution channels are needed to ensure that the products are potent and effective at the point of use. The technologies used to manufacture different types of vaccines can strongly affect vaccine cost, ease of industrial scale-up, stability, and, ultimately, worldwide availability. The complexity of manufacturing is compounded by the need for different formulations in different countries and age-groups.

Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation.

Rhinoviruses cause serious morbidity and mortality as the major etiological agents of asthma exacerbations and the common cold. A major obstacle to understanding disease pathogenesis and to the development of effective therapies has been the lack of a small-animal model for rhinovirus infection. Of the 100 known rhinovirus serotypes, 90% (the major group) use human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor and do not bind mouse ICAM-1; the remaining 10% (the minor group) use a member of the low-density lipoprotein receptor family and can bind the mouse counterpart.

Towards a dengue vaccine: progress to date and remaining challenges.

The increased incidence and extended geographical reach of Dengue virus over the past two decades have made the development of an effective vaccine an international urgency. Various strategies are being pursued, including live, vectored and killed/recombinant preparations. For all approaches, the challenge is to induce a broad durable immune response against all four serotypes of Dengue virus simultaneously whilst avoiding the possible exacerbation of risk of developing the severe forms of disease through incomplete or modified responses.

Vaccine renaissance.

Vaccines are one of the most useful and cost-effective tools for reducing the morbidity and mortality that are associated with infectious diseases. Here, Jeffrey Almond discusses the selection of articles in this Focus issue, in the context of the challenges and opportunities facing vaccine developers today.

Rational design of genetically stable, live-attenuated poliovirus vaccines of all three serotypes: relevance to poliomyelitis eradication.

The global eradication of poliomyelitis caused by wild-type virus is likely to be completed within the next few years, despite immense logistic and political difficulties, and may ultimately be followed by the cessation of vaccination. However, the existing live-attenuated vaccines have the potential to revert to virulence, causing occasional disease, and viruses can be shed by immunocompromised individuals for prolonged periods of time. Moreover, several outbreaks of poliomyelitis have been shown to be caused by viruses derived from the Sabin vaccine strains.

Serum IgG mediates mucosal immunity against rotavirus infection.

We evaluated the protective role of passively transferred circulating antibodies in protecting non-human primates against experimental rotavirus infection. Pooled sera with rotavirus-specific IgG titers that were either high (1:10,000), intermediate (1:300), or negative (< 1:25) were infused i.v.

Therapeutic vaccines against infectious diseases.

Therapeutic vaccines against chronic infectious diseases aim at eliciting broad humoral and cellular immune responses against multiple target antigens. Importantly, the development of such vaccines will help to establish surrogate markers of protection in humans and thus will augment the subsequent development of efficient prophylactic vaccines. A combination of synthetic small-molecule drugs and immunotherapeutics is likely to represent a powerful means of controlling chronic infections in the future.

Delivery technologies for human vaccines.

There is currently intense research activity aimed at the development of new delivery systems for vaccines. The goal is to identify optimal methods for presenting target antigens to the immune system in a manner that will elicit immune responses appropriate for protection against, or treatment of, a specific disease. Several different approaches to this general goal have been developed, some are empirical and remain poorly understood, others are more rational, being based, for example, on mimicking natural infections in vivo or on targeting particular features of the immune system.

Mapping the binding domains on decay accelerating factor (DAF) for haemagglutinating enteroviruses: implications for the evolution of a DAF-binding phenotype.

Decay accelerating factor (DAF) functions as a cell attachment receptor for a wide range of human enteroviruses, the interaction accounting for the haemagglutination phenotype exhibited by many members of this family. Haemagglutination inhibition assays using purified truncated soluble DAF (sDAF) receptors and short consensus repeat (SCR) domain-specific antibodies have been used to determine the domain(s) of DAF to which the viruses bind. Further sDAF-mediated virus neutralization and biosensor analysis have been used to confirm the virus-binding domains of DAF.