Emulsion and liposome-based adjuvanted R21 vaccine formulations mediate protection against malaria through distinct immune mechanisms.

Adjuvanted protein vaccines offer high efficacy, yet most potent adjuvants remain proprietary. Several adjuvant compounds are being developed by the Vaccine Formulation Institute in Switzerland for global open access clinical use. In the context of the R21 malaria vaccine, in a mouse challenge model, we characterize the efficacy and mechanism of action of four Vaccine Formulation Institute adjuvants: two liposomal (LQ and LMQ) and two squalene emulsion-based adjuvants (SQ and SMQ), containing QS-21 saponin (Q) and optionally a synthetic TLR4 agonist (M).

Neutrophilia, lymphopenia and myeloid dysfunction: a living review of the quantitative changes to innate and adaptive immune cells which define COVID-19 pathology.

Destabilization of balanced immune cell numbers and frequencies is a common feature of viral infections. This occurs due to, and further enhances, viral immune evasion and survival. Since the discovery of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which manifests in coronavirus disease 2019 (COVID-19), a great number of studies have described the association between this virus and pathologically increased or decreased immune cell counts.

T cell phenotypes in COVID-19 - a living review.

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development.

TLR Agonists as Vaccine Adjuvants Targeting Cancer and Infectious Diseases.

Modern vaccines have largely shifted from using whole, killed or attenuated pathogens to being based on subunit components. Since this diminishes immunogenicity, vaccine adjuvants that enhance the immune response to purified antigens are critically needed. Further advantages of adjuvants include dose sparing, increased vaccine efficacy in immunocompromised individuals and the potential to protect against highly variable pathogens by broadening the immune response.

Inflammasome-Mediated Immunogenicity of Clinical and Experimental Vaccine Adjuvants.

In modern vaccines, adjuvants can be sophisticated immunological tools to promote robust and long-lasting protection against prevalent diseases. However, there is an urgent need to improve immunogenicity of vaccines in order to protect mankind from life-threatening diseases such as AIDS, malaria or, most recently, COVID-19. Therefore, it is important to understand the cellular and molecular mechanisms of action of vaccine adjuvants, which generally trigger the innate immune system to enhance signal transition to adaptive immunity, resulting in pathogen-specific protection.

Technological Approaches for Improving Vaccination Compliance and Coverage.

Vaccination has been well recognised as a critically important tool in preventing infectious disease, yet incomplete immunisation coverage remains a major obstacle to achieving disease control and eradication. As medical products for global access, vaccines need to be safe, effective and inexpensive. In line with these goals, continuous improvements of vaccine delivery strategies are necessary to achieve the full potential of immunisation.

Investigating the Effect of Encapsulation Processing Parameters on the Viability of Therapeutic Viruses in Electrospraying.

The ability of viruses to introduce genetic material into cells can be usefully exploited in a variety of therapies and also vaccination. Encapsulating viruses to limit inactivation by the immune system before reaching the desired target and allowing for controlled release is a promising strategy of delivery. Conventional encapsulation methods, however, can significantly reduce infectivity.

Publisher Correction: Adjuvanting a viral vectored vaccine against pre-erythrocytic malaria.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Vaccination with the Staphylococcus aureus secreted proteins EapH1 and EapH2 impacts both S. aureus carriage and invasive disease.

Introduction: There is a need for an efficacious vaccine reducing infections due to Staphylococcus aureus, a common cause of community and hospital infection. Infecting organisms originate from S. aureus populations colonising the nares and bowel.

Development of persistent gastrointestinal S. aureus carriage in mice.

One fifth to one quarter of the human population is asymptomatically, naturally and persistently colonised by Staphylococcus aureus. Observational human studies indicate that although the whole population is intermittently exposed, some individuals lose S. aureus rapidly.

Adjuvanting a viral vectored vaccine against pre-erythrocytic malaria.

The majority of routinely given vaccines require two or three immunisations for full protective efficacy. Single dose vaccination has long been considered a key solution to improving the global immunisation coverage. Recent infectious disease outbreaks have further highlighted the need for vaccines that can achieve full efficacy after a single administration.

The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens.

A persistent goal of vaccine development is the enhancement of the immunogenicity of antigens while maintaining safety. One strategy involves alteration of the presentation of the antigen by combining antigens with a multimeric scaffold. Multi-antigen vaccines are under development, and there are presently far more candidate antigens than antigen scaffolding strategies.

Next generation vaccines: single-dose encapsulated vaccines for improved global immunisation coverage and efficacy.

Objectives: Vaccination is considered the most successful health intervention; yet incomplete immunisation coverage continues to risk outbreaks of vaccine preventable diseases worldwide. Vaccination coverage improvement through a single-dose prime-boost technology would revolutionise modern vaccinology, impacting on disease prevalence, significantly benefiting health care and lowering economic burden of disease.

Key Findings: Over the past 30 years, there have been efforts to develop a single-dose delayed release vaccine technology that could replace the repeated prime-boost immunisations required for many current vaccines.

Immune responses associated with homologous protection conferred by commercial vaccines for control of avian pathogenic Escherichia coli in turkeys.

Avian pathogenic Escherichia coli (APEC) infections are a serious impediment to sustainable poultry production worldwide. Licensed vaccines are available, but the immunological basis of protection is ill-defined and a need exists to extend cross-serotype efficacy. Here, we analysed innate and adaptive responses induced by commercial vaccines in turkeys.

Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

Background: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens.

A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years.

Background: Current influenza vaccines have reduced immunogenicity and are of uncertain efficacy in older adults. We assessed the safety and immunogenicity of MVA-NP+M1, a viral-vectored influenza vaccine designed to boost memory T cell responses, in a group of older adults.

Methods: Thirty volunteers (aged 50-85) received a single intramuscular injection of MVA-NP+M1 at a dose of 1·5×10(8) plaque forming units (pfu).

Small cationic DDA:TDB liposomes as protein vaccine adjuvants obviate the need for TLR agonists in inducing cellular and humoral responses.

Most subunit vaccines require adjuvants in order to induce protective immune responses to the targeted pathogen. However, many of the potent immunogenic adjuvants display unacceptable local or systemic reactogenicity. Liposomes are spherical vesicles consisting of single (unilamellar) or multiple (multilamellar) phospholipid bi-layers.

Mixed vector immunization with recombinant adenovirus and MVA can improve vaccine efficacy while decreasing antivector immunity.

Substantial protection can be provided against the pre-erythrocytic stages of malaria by vaccination first with an adenoviral and then with an modified vaccinia virus Ankara (MVA) poxviral vector encoding the same ME.TRAP transgene. We investigated whether the two vaccine components adenovirus (Ad) and MVA could be coinjected as a mixture to enhance protection against malaria.

The requirement for potent adjuvants to enhance the immunogenicity and protective efficacy of protein vaccines can be overcome by prior immunization with a recombinant adenovirus.

A central goal in vaccinology is the induction of high and sustained Ab responses. Protein-in-adjuvant formulations are commonly used to achieve such responses. However, their clinical development can be limited by the reactogenicity of some of the most potent preclinical adjuvants and the cost and complexity of licensing new adjuvants for human use.

CD8+ T effector memory cells protect against liver-stage malaria.

Identification of correlates of protection for infectious diseases including malaria is a major challenge and has become one of the main obstacles in developing effective vaccines. We investigated protection against liver-stage malaria conferred by vaccination with adenoviral (Ad) and modified vaccinia Ankara (MVA) vectors expressing pre-erythrocytic malaria Ags. By classifying CD8(+) T cells into effector, effector memory (T(EM)), and central memory subsets using CD62L and CD127 markers, we found striking differences in T cell memory generation.

Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1.

Background: Influenza A viruses cause occasional pandemics and frequent epidemics. Licensed influenza vaccines that induce high antibody titers to the highly polymorphic viral surface antigen hemagglutinin must be re-formulated and readministered annually. A vaccine providing protective immunity to the highly conserved internal antigens could provide longer-lasting protection against multiple influenza subtypes.

Peptide-major histocompatibility complex dimensions control proximal kinase-phosphatase balance during T cell activation.

T cell antigen recognition requires binding of the T cell receptor (TCR) to a complex between peptide antigen and major histocompatibility complex molecules (pMHC), and this recognition occurs at the interface between the T cell and the antigen-presenting cell. The TCR and pMHC molecules are small compared with other abundant cell surface molecules, and it has been suggested that small size is functionally important. We show here that elongation of both mouse and human MHC class I molecules abrogates T cell antigen recognition as measured by cytokine production and target cell killing.

Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor.

HIV's considerable capacity to vary its HLA-I-restricted peptide antigens allows it to escape from host cytotoxic T lymphocytes (CTLs). Nevertheless, therapeutics able to target HLA-I-associated antigens, with specificity for the spectrum of preferred CTL escape mutants, could prove effective. Here we use phage display to isolate and enhance a T-cell antigen receptor (TCR) originating from a CTL line derived from an infected person and specific for the immunodominant HLA-A(*)02-restricted, HIVgag-specific peptide SLYNTVATL (SL9).

Ectopic expression of P-cadherin correlates with promoter hypomethylation early in colorectal carcinogenesis and enhanced intestinal crypt fission in vivo.

P-cadherin is normally expressed in the basal layer of squamous epithelia and absent from the healthy intestine and colon. We have previously shown it to be expressed in all inflamed, hyperplastic, and dysplastic intestinal and colonic mucosa. This study aimed to better understand the mechanisms controlling the expression of P-cadherin and the biological effects of its ectopic presence in the intestine and colon.

The HLA A*0201-restricted hTERT(540-548) peptide is not detected on tumor cells by a CTL clone or a high-affinity T-cell receptor.

Tumor-associated human telomerase reverse transcriptase (hTERT) is expressed in >85% of human tumors but not in most normal cells. As a result, this antigen has received considerable attention from those interested in cancer immunotherapy. Specifically, there has been strong interest in MHC class I-associated peptides derived from hTERT because these are expressed on the cell surface and thus may enable the targeting of tumor cells.