Vaccine最新文献

Influenza A viruses (IAV) of subtypes H1N1, H1N2, and H3N2 are endemic in US domestic swine populations and contribute to significant economic losses annually and pose a persistent pandemic threat. Adjuvanted, whole-inactivated virus (WIV) vaccines are the primary countermeasure to control IAV in swine. The compositions of these vaccines are matched for hemagglutinin (HA) strain and content, often ignoring the other IAV glycoprotein, the neuraminidase (NA). The IAV NA is immunogenic and antibodies targeting epitopes adjacent to the active site have been shown to inhibit the sialidase activity of NA thereby reducing virus replication and shedding. To assess the ability of neuraminidase inhibiting (NAI) antibodies induced from WIV administration to protect swine from challenge with IAV containing homologous and heterologous NA, we produced WIV composed of viruses with an irrelevant mismatched H9 HA but expressing NA proteins from two predominant clades (N2-2002A.2 and N22002B.2) currently circulating in US domestic swine populations. Pigs that received two doses of H9N2 WIV developed vaccine-specific neuraminidase inhibition antibodies and when challenged with a wild-type H3N2 virus containing homologous NA, displayed reduced virus shedding in the upper respiratory tract and decreased virus titers in the lung compared to unvaccinated controls. Pigs challenged with H3N2 containing a heterologous NA also had reduced virus titers in the nasal swab and BALF samples. Together these results show that NAI antibodies cross-protected across phylogenetic clades and reduced virus replication and shedding in swine.

Background: Surveillance systems for monitoring and reporting adverse events following immunisation (AEFI) and adverse events of special interest (AESI) are vital in understanding safety profiles of post-marketed vaccines. Evaluation of surveillance systems is necessary for systems strengthening. We conducted the first evaluation of the South African AEFI surveillance system in its current form, established in 2018.

Methods: Using CDC guidelines for evaluation of surveillance systems, we conducted a cross-sectional evaluation of system attributes, including quantitative analyses of AEFI/AESI data from 17 May 2021 to 31 December 2022 and qualitative analyses through semi-structured interviews with AEFI surveillance personnel. Findings were used to generate recommendations for system strengthening.

Results: The system collects and manages AEFI data, employs investigative tools and has an established AEFI review committee conducting causality assessment, thus meeting WHO minimal capacity for vaccine safety. System adaptation through inclusion of digital applications facilitated public reporting, whilst increasing complexity of database management. Respondents demonstrated engagement with the system through accounts of their roles in AEFI surveillance. Between 17 May 2021 and 31 December 2022, 37,537,009 COVID-19 vaccine doses (BNT162b2 and Ad26.COV2·S) were administered, and 3846 AEFI reported in relation to these vaccines (reporting rate: 10.2/100,000 doses). AEFI reporting rates varied considerably across provinces, ranging from 1.6 to 59.5 AEFI/100,000 doses. In this time period 283 AEFI were reported in relation to non-COVID-19 vaccines. By 31 December 2022, 73.5 % of severe cases that were investigated were causality assessed.

Conclusion: We observed a functional, useful, flexible system with high reported stakeholder and public acceptability levels. System challenges included low reporting rates from particular provinces, weak co-ordination between paper and digital reporting and human resource constraints. Recommendations include integration of paper-based and digital surveillance reporting systems to enhance signal detection and eliminate data duplication, provision of dedicated human and financial resources at provincial level and inclusion of active AEFI surveillance through cohort event monitoring.

Lung cancer is one of the most lethal cancers. Unfortunately, respiratory tract infections are very common in lung cancer patients, delaying appropriate anticancer therapy. To increase therapy efficiency, in this study we examined the effect of 13-Valent Pneumococcal Conjugate Vaccine on the immune response in lung cancer patients, which indirectly affects the success of anticancer therapy. The study was done using biochemical tests and Fourier Transform InfraRed (FTIR) spectroscopy. For this purpose, serum from lung cancer patients aged 52 ± 9 years (III and IV clinical stage; 79 %; n = 103) before and seven as well as 30 days after vaccination was collected. Obtained results showed increasing concentrations of immunoglobulin IgG and IgG2 groups in patients after vaccination in comparison with group before vaccination. This result was confirmed by FTIR spectroscopy, where higher absorbances of amides vibrations were observed after vaccination. Interestingly, lack of differences in the amides absorbances between patients 7 and 30 days after vaccination were noticed. FTIR spectra also showed changes in the ratio between amide I and amide III as well as between amide II and amide III in the groups of patients after vaccination. From deconvolution of made I range (1600 cm^-1-1700 cm^-1) decrease of the ratio between α-helix and β-sheet around 0.05 was noticed in serum collected from patients after vaccination in comparison with patients before vaccination. Using Principal Component Analysis (PCA) analysis of FTIR data it was observed that serum collected from all three analyzed groups of samples was possible to differentiate. The highest accuracy in differentiation group of samples before and 7 days after vaccination was visible in amide I, while before and 30 days after vaccination using amide II. Correlation between immunoglobulin IgG and IgG2 concentrations obtained by biochemical assays and FTIR were noticed only in the group of serum collected 30 days after vaccination, which suggested that FTIR spectroscopy reflects biochemical data.

Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that infects immunocompromised individuals, especially in the hospital setting. This bacterium is an important pathogen in people with weakened immune systems, injuries, and other underlying physiologic dysfunctions. P. aeruginosa is responsible for up to 20 % of all hospital-acquired pneumonias. It is one of the major causes of nosocomial infections and has been noted to be one of the most common bacteria co-infecting patients with COVID-19 or causing super-infections following COVID-19 infections. Despite improvements in antimicrobial therapy and hospital care, P. aeruginosa bacteremia and pneumonia remain fatal in about 30 % of cases. P. aeruginosa is also the leading cause of chronic life-threatening lung infections in cystic fibrosis patients. This bacterium is naturally antibiotic resistant, and infections are notoriously difficult to treat once established, with no vaccine available. We have previously shown that elongation factor-Tu (EF-Tu), a protein best known for its role in protein synthesis, is surface exposed on P. aeruginosa. As this protein is highly expressed, evolutionally conserved, and essential, we hypothesized it would make a good vaccine target. In this study, we found that P. aeruginosa EF-Tu is immunogenic in people, and that mice can develop an immune response following immunization with recombinant P. aeruginosa EF-Tu. Furthermore, immunized mice were protected from subsequent P. aeruginosa pneumonia and transfer of this vaccine antisera to naïve mice resulted in decreased colonization. Altogether these findings support the consideration of EF-Tu as a new vaccine candidate against P. aeruginosa.

Purpose: Vaccination rates are significantly lower among adolescents living in rural areas compared to those living in urban areas. The objective of this study was to understand the factors contributing to disparities in vaccination between adolescents in rural compared to urban areas.

Methods: Semi-structured qualitative interviews were conducted with parents and providers in 16 rural and 4 urban counties of Colorado. Interview questions followed the socioecological model of health and addressed personal, interpersonal, community, and environment/structural barriers and facilitators that impact adolescent vaccination rates. Qualitative content analysis with a directed content analysis approach was used. Urban and rural interviews were compared to identify barriers unique to rural communities.

Findings: Reported barriers included lack of vaccine access at primary care, lack of routine preventive care utilization, the need to take off time from work and school, and misinformation about vaccines. Barriers that were unique to rural communities included structural barriers such as lack of evening and weekend appointments, providers not stocking vaccines, short provider tenures, and costs; logistical barriers such as the need for multiple visits to multiple locations and distance and travel time; and beliefs and behaviors such as an overreliance on sports physicals (in lieu of preventive visits) and natural lifestyle cultures.

Conclusions: There are unique challenges to adolescent vaccination in rural areas that contribute to fewer adolescents receiving their recommended vaccines. Addressing structural barriers may address this disparity.

Feline herpesvirus type 1 (FHV) and feline calicivirus (FCV) are significant pathogens causing upper respiratory tract disease in cats. Existing inactivated or modified live vaccines against FCV and FHV face limitations in safety and efficacy. To overcome these challenges, a recombinant strain FHV ΔgI/gE-FCV VP1 was developed by deleting the gI/gE gene and concurrently expressing FCV VP1, using the FHV WX19 strain as the parental virus. Results indicated the presence of FCV VP1 in FHV ΔgI/gE-FCV VP1-infected CRFK cells, confirmed through protein blotting and immunofluorescence assays and virus-like particles (VLPs) of FCV were observed using transmission electron microscopy. For efficacy in cats, each animal received intranasal vaccination with 1 mL of FHV ΔgI/gE-FCV VP1 at 10⁶ TCID₅₀. Following completion of vaccination on day 28, animals were exposed to a potent FCV strain. Assessments included clinical signs, nasal shedding, virus neutralizing antibodies, cytokine expression and postmortem histological testing. All vaccinations with FHV ΔgI/gE-FCV VP1 were deemed safe, with significantly reduced clinical disease scores, pathological changes and viral nasal shedding following infection and robust immune responses were induced. These findings collectively suggest the effectiveness of FHV-based recombinant vaccines in preventing FCV infections.

A vaccine effective against both SARS-CoV-2 and influenza A (IAV) viruses could represent a cost-effective strategy to reduce their combined public health burden as well as potential complications arising from co-infection. Based on previous findings that full-length SARS-CoV-2 spike (S) expression can induce high-level, enveloped VLP (eVLP) production in CHO cells, we tested whether IAV H1N1 hemagglutinin (H1) and neuraminidase (N1) could also be displayed on these particles. We found that co-incorporation of the IAV surface antigens in spike VLPs (S-VLPs) was highly efficient: upon transient co-expression of S + H1 or S + H1 + N1 in CHO cells, the resulting VLPs contained similar amounts of the SARS-CoV-2 S and IAV antigens. The self-assembled bivalent (S/H1) and trivalent (S/H1/N1) VLPs released into the culture media were purified by single-step chromatography using a S-VLP affinity resin. Western blot analysis and immuno‑gold labeling transmission electron microscopy (TEM) of purified VLPs confirmed the coexistence of S, H1 and N1 antigens in the same particles. Finally, we demonstrated that two doses of adjuvanted bivalent and trivalent VLPs elicit specific functional antibodies and cellular immunity in a mouse model, suggesting potential for combined SARS-CoV-2/IAV vaccine development.

Virtual reality for routine immunisations in needle phobic children with and without developmental disabilities: a pilot study.

Background: Virtual Reality (VR) headsets can improve needle procedure success and experiences for children, but they have not been evaluated to support immunisation in children with anxiety and behavioural challenges. This study assessed the feasibility and acceptability of VR for immunisation in children with needle phobia, including children with and without developmental disabilities.

Methods: A mixed method pilot study was conducted at the Royal Children's Hospital, Melbourne. Children with needle phobia aged 4-14 years scheduled for immunisation with distraction and conscious sedation were eligible. VR was offered to children with needle anxiety and/or developmental disabilities before and during immunisation in addition to standard care. Children and caregivers completed electronic surveys pre- and post-immunisation, followed by qualitative interviews post-immunisation. Clinicians completed post-immunisation surveys. Primary outcomes were feasibility and acceptability of VR according to children, caregivers and clinicians.

Results: Between May and December 2022, we screened 54 children and included 30; 15 with and 15 without developmental disability. Preparation to use VR took less than five minutes for most children (24/30; 80 %). Twenty nine (96 %) used VR immediately before immunisation, and 17 (57 %) continued using it during immunisation (7 with developmental disability, 10 without). Twenty seven (90 %) children were immunised successfully, with a small reduction in required sedation. Of those who used VR during immunisation, 16/17 (94 %) reported a more positive overall experience. Of those who only used VR before immunisation, 3/13 (23 %) still reported benefit. VR was therefore described as beneficial for 19/30 (63 %) participants (9 with developmental disability, 10 without). Caregivers reported willingness to use VR in future immunisation encounters for 23/30 (77 %) children (11 with developmental disability, 12 without).

Discussion: This pilot study suggests VR was feasible and acceptable for many children with needle phobia, both with and without developmental disability. These findings will inform a randomised controlled trial to assess effectiveness.

Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV. Adults aged ≥60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022-2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with ≥3 and ≥ 2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post-vaccination respectively, and SAEs for the entire study period. In total, 18,348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9 % (95 % CI: -16.1; 71.9) against RSV-associated LRTD with ≥3 symptoms, 59.0 % (95 % CI: 34.7; 74.3) against LRTD with ≥2 symptoms, and 48.8 % (95 % CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with ≥3 symptoms since the lower bound of the 95 % CI was below 20 %, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified. MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases. Trial Registration:Clinicaltrials.gov Identifier NCT05238025 (Registered February 14, 2022).