Therapeutic Advances in Vaccines and Immunotherapy最新文献

CD8⁺ T-cell exhaustion is a dysfunctional state that is regulated through the expression of inhibitory checkpoint receptor genes including the cytotoxic T-lymphocyte-associated antigen 4, programmed death 1, and DNA methylation of effector genes interferon-γ, perforin, and granzyme B. Different strategies have been used to reverse T-cell exhaustion, which is an adverse event of checkpoint inhibitor blockade. Here, we present the mechanisms by which DNA methyltransferase inhibitors and Simian virus 40 large T antigen through viral mimicry can promote the reversion of exhausted CD8⁺ T cells. We examine how these pharmacological strategies can work together to improve the clinical efficacy of immunotherapies.

Influenza continues to cause severe illness in millions and deaths in hundreds of thousands annually. Vaccines are used to prevent influenza outbreaks, however, the influenza virus mutates and annual vaccination is required for optimal protection. Vaccine effectiveness is also affected by other potential factors such as the human immune system, a mismatch with the chosen candidate virus, and egg adaptation associated with egg-based vaccine production. This article reviews the influenza vaccine development process and describes the implications of the changes to the cell-culture process and vaccine strain recommendations by the World Health Organization since the 2017 season. The traditional manufacturing process for influenza vaccines relies on fertilized chicken eggs that are used for vaccine production. Vaccines must be produced in large volumes and the complete process requires approximately 6 months for the egg-based process. In addition, egg adaptation of seed viruses occurs when viruses adapt to avian receptors found within eggs to allow for growth in eggs. These changes to key viral antigens may result in antigenic mismatch and thereby reduce vaccine effectiveness. By contrast, cell-derived seed viruses do not require fertilized eggs and eliminate the potential for egg-adapted changes. As a result, cell-culture technology improves the match between the vaccine virus strain and the vaccine selected strain, and has been associated with increased vaccine effectiveness during a predominantly H3N2 season. During the 2017-2018 influenza season, a small number of studies conducted in the United States compared the effectiveness of egg-based and cell-culture vaccines and are described here. These observational and retrospective studies demonstrate that inactivated cell-culture vaccines were more effective than egg-based vaccines. Adoption of cell-culture technology for influenza vaccine manufacturing has been reported to improve manufacturing efficiency and the additional benefit of improving vaccine effectiveness is a key factor for future policy making considerations.

Background: Hepatitis B virus (HBV) infection is highly endemic in Nigeria. The primary objective of this study is to describe the knowledge, self-reported vaccination status, and intention of healthcare workers to receive hepatitis B vaccine at a tertiary referral center in conflict-ravaged northeastern Nigeria.

Methods: This was cross-sectional analytical study among medical practitioners, nurses, laboratory workers, health attendants, pharmacists, and radiographers working at Federal Medical Center Nguru, Yobe State. Written informed consent was obtained from all study participants. Data were obtained using questionnaires and entered into a Microsoft Excel spreadsheet, cleaned and analyzed using JMP Pro software.

Results: Of the 182 participants, we found that 151 (82.97%), 81 (44.51%), 85 (46.70%), and 33 (18.13%) had good knowledge of HBV, good knowledge of hepatitis B vaccine, were vaccinated against HBV by the least dose, and had a complete hepatitis B vaccination status, respectively. The lack of availability of the vaccine was the main reason for not receiving the vaccine among the unvaccinated 36/91 (39.56%), followed by not knowing where to access the vaccine 19/91 (20.88%).

Conclusion: The study highlights the need for strategies to ensure the availability of hepatitis B vaccine in conflict settings and need for vaccinology training given the suboptimal level of awareness and uptake of the hepatitis B vaccine among the healthcare workers.

Background: Immunization against Neisseria meningitidis is important for public health. Vaccines composed of cross-reactivity antigens avoid strain-specific responses, ensuring more comprehensive protection.

Methods: The cross-reactivity between three strains from the last outbreak of N. meningitidis in Brazil was assessed in our studies, using enzyme-linked immunosorbent assay (ELISA) and immunoblotting assays.

Results: Both assays verifed a similar humoral response between the strains evaluated. Patterns of antigen recognition differed with each dose evaluated.

Conclusions: We observed that immunization with N. meningitidis B outer membrane vesicles (OMVs) led to the production of antibodies that recognized antigens of heterologous strains, indicating possible protection against these evaluated strains.

The influenza virus causes significant human morbidity and mortality annually and poses a pandemic threat. In addition, the virus frequently mutates, contributing to thousands of identified strains. Current influenza vaccine solutions are strain specific, target existing strains, and achieve only approximately 40% vaccine effectiveness (VE). The need for broadly protective Universal Influenza Vaccines (UIVs) is clear. UIV research and development efforts focus on widely conserved (i.e. not strain specific) influenza epitopes. The most clinically advanced UIV candidate, the Multimeric-001 (M-001), is currently undergoing a pivotal, clinical efficacy, phase III trial. Completed clinical trials indicate M-001 is safe, well tolerated, and immunogenic to a broad range of influenza strains. Additional candidates are also under development, supported by public and private funding. Research results suggest that it is only a matter of time until a broadly protective influenza vaccine is approved for licensure.

Background: Peanut allergy has become an important public health issue. It can be the cause of severe reactions and also the trigger of significant anxiety for the allergic individual, especially with regards to the risk of unintentional accidental exposures. Peanut oral immunotherapy (POIT) is a newly developed treatment approach that has been shown to be highly effective in multiple research studies and has been associated with an acceptable safety profile. This treatment modality is likely to become more mainstream in the next few years with new commercial entities pursuing United States Food and Drug Administration approval for relevant products and multiple providers offering various forms of immunotherapy in their practices.

Methods: The aim of our study was to obtain an accurate assessment of goals of treatment as well as concerns and barriers from families considering POIT in either the research or clinical setting. A single clinician allergist met with all the families and conducted semi-structured interviews on POIT. Families were provided with standardized written information on POIT prior to the consultation, which was used as a formalized instrument to communicate treatment protocols. Conversations were not recorded, but collected information was scribed by a second clinician who did not actively participate in the consultation. Scribed information was coded by the investigators. Thematic analysis identified common topics emerging from the discussions.

Results: We report on the results of 92 consecutive family consultations on POIT conducted over a period of 1 year. Approximately 50% of the families had already researched POIT online, with 25% of families reported being part of Facebook parent groups. Groups identified the following areas as the most important considerations: efficacy, practical information, safety, benefits and goals, eligibility criteria and support in making the right decision. For all families pursuing POIT for their child, the initial goal was achieving protection from accidental exposure and cross-contamination and for approximately one-quarter, consumption of high peanut doses was the ultimate goal.

Conclusion: Our research adds to the limited available data in this area and provides information that may be used as an initial platform for clinical consultations and shared decision-making in POIT. Obtaining a better understanding of patients' expectations and concerns will hopefully facilitate this process, enabling more fruitful and engaging interactions between families and healthcare providers in the field of food allergy.

Recent immunotherapy advances have convincingly demonstrated complete tumour removal with long-term survival. These impressive clinical responses have rekindled enthusiasm towards immunotherapy and tumour antigen vaccination providing 'cures' for melanoma and other cancers. However, many patients still do not benefit; sometimes harmed by severe autoimmune toxicity. Checkpoint inhibitors (anti-CTLA4; anti-PD-1) and interleukin-2 (IL-2) are 'pure immune drivers' of pre-existing immune responses and can induce either desirable effector-stimulatory or undesirable inhibitory-regulatory responses. Why some patients respond well, while others do not, is presently unknown, but might be related to the cellular populations being 'driven' at the time of dosing, dictating the resulting immune response. Vaccination is in-vivo immunotherapy requiring an active host response. Vaccination for cancer treatment has been skeptically viewed, arising partially from difficulty demonstrating clear, consistent clinical responses. However, this article puts forward accumulating evidence that 'vaccination' immunomodulation constitutes the fundamental, central, intrinsic property associated with antigen exposure not only from exogenous antigen (allogeneic or autologous) administration, but also from endogenous release of tumour antigen (autologous) from in-vivo tumour-cell damage and lysis. Many 'standard' cancer therapies (chemotherapy, radiotherapy etc.) create waves of tumour-cell damage, lysis and antigen release, thus constituting 'in-vivo vaccination' events. In essence, whenever tumour cells are killed, antigen release can provide in-vivo repeated vaccination events. Effective anti-tumour immune responses require antigen release/supply; immune recognition, and immune responsiveness. With better appreciation of endogenous vaccination and immunomodulation, more refined approaches can be engineered with prospect of higher success rates from cancer therapy, including complete responses and better survival rates.

Highly pathogenic avian influenza viruses (HPAIVs), originating from the A/goose/Guangdong/1/1996 H5 subtype, naturally circulate in wild-bird populations, particularly waterfowl, and often spill over to infect domestic poultry. Occasionally, humans are infected with HPAVI H5N1 resulting in high mortality, but no sustained human-to-human transmission. In this review, the replication cycle, pathogenicity, evolution, spread, and transmission of HPAIVs of H5Nx subtypes, along with the host immune responses to Highly Pathogenic Avian Influenza Virus (HPAIV) infection and potential vaccination, are discussed. In addition, the potential mechanisms for Highly Pathogenic Avian Influenza Virus (HPAIV) H5 Reassorted Viruses H5N1, H5N2, H5N6, H5N8 (H5Nx) viruses to transmit, infect, and adapt to the human host are reviewed.