Therapeutic Advances in Vaccines and Immunotherapy最新文献

This study was a phase III, multicenter, double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a seasonal trivalent split, inactivated influenza vaccine (TIV) in healthy Serbian adults between the ages of 18 and 65 years. This egg-based vaccine was manufactured by the Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia. A total of 480 participants were assigned randomly in a ratio of 2:1 to receive a single intramuscular dose (0.5 ml) of the vaccine (15 µg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Participants were monitored for safety, including solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). No SAEs related to vaccination were reported. Injection site pain (51.3%), injection site tenderness (40.4%), tiredness (17.0%), and headache (15.1%) were the most commonly reported solicited events in the vaccine group. Incidence of related unsolicited AEs was low (1.3%) among vaccinees. Hemagglutinin inhibition (HAI) titers were measured before and 21 days after vaccination in 151 participants. Overall, HAI seroconversion rates to H1 and H3 were observed in 90.1% and 76.2% of vaccinees, respectively. For B antigen, it was 51.5%, likely due to high pre-vaccination titers. Post-vaccination seroprotection rates were in the range of 78.2-95.0% for the three antigens. Post-vaccination geometric mean titers (GMT) were at least 3.8 times higher than baseline levels for all the three strains among vaccinees. Overall, the study showed that the vaccine was safe and well tolerated, and induced a robust immune response against all three vaccine strains. ClinicalTrials.gov identifier: NCT02935192, October 17, 2016.

Background: Neisseria meningitidis is the main cause of bacterial meningitis in Brazil, where the main serogroups isolated are B and C; however, the serogroup W has recently emerged. LPS and type IV pili are important virulence factors that increase meningococci pathogenicity.

Methods: The characterization of Lipopolysaccharide (LPS) and type IV pili in 19 meningococci strains of serogroup B, 21 of serogroup C, 45 of serogroup W and 28 of serogroup Y, isolated in Brazil between 2011 and 2017, was conducted using the Enzyme-linked Immunosorbent Assay (Dot- ELISA) technique and monoclonal antibodies.

Results: We would like to emphasize the importance of characterizing relevant antigens, such as pili and LPS, the use of monoclonal antibodies to support it, and how such studies improve vaccine development and monitoring. Most of the strains studied presented L3,7,9 LPS and type IV pili; both antigens are associated with the capacity to cause invasive disease.

Conclusion: Due to the impact of meningococcal disease, it is important to maintain and improve vaccine studies. Epitopes characterization provides data about the virulence of circulating strains. The use of monoclonal antibodies and serological techniques are relevant and support vaccine development.

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.