Search

Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although vaccines against SARS-CoV-2 based on mRNA and adenoviral vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are required to meet global demand. Protein subunit vaccines formulated with appropriate adjuvants represent an approach to address this urgent need. The receptor binding domain (RBD) is a key target of SARS-CoV-2 neutralizing antibodies but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists alone or formulated with aluminum hydroxide (AH) and benchmarked them against AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that an AH and CpG adjuvant formulation (AH:CpG) produced an 80-fold increase in anti-RBD neutralizing antibody titers in both age groups relative to AH alone and protected aged mice from the SARS-CoV-2 challenge. The AH:CpG-adjuvanted RBD vaccine elicited neutralizing antibodies against both wild-type SARS-CoV-2 and the B.1.351 (beta) variant at serum concentrations comparable to those induced by the licensed Pfizer-BioNTech BNT162b2 mRNA vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and enhanced cytokine and chemokine production in human mononuclear cells of younger and older adults. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups. A vaccine for the ages: Vaccines against SARS-CoV-2 are especially important for protecting older adults who are at the highest risk of developing severe COVID-19. To address this, Nanishi et al. tested a receptor binding domain (RBD) protein subunit vaccine with a variety of adjuvants to find which combination best protected aged mice. The authors found that combining RBD with aluminum hydroxide (AH) and CpG resulted in a highly immunogenic vaccine that was protective in young and aged mice. The authors also showed that AH:CpG induced robust innate immune responses in peripheral blood mononuclear cells isolated from older adults. This vaccine is also scalable and could be deployed to low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Background Japanese encephalitis (JE) is the leading cause of viral encephalitis with high mortality and morbidity in Asia. In Japan, however, the active recommendation of JE vaccine was retracted in 2005 because of the potential risk of acute disseminated encephalomyelitis. We aimed to determine the recent incidence of childhood-onset JE after the domestic change of vaccination policy in Japan, and to analyze the clinical features of affected children. Methods A retrospective nationwide survey was conducted for pediatric patients with JE in Japan from 1995 to 2015. The national surveillance system was used to identify the pediatric patients with JE. Follow-up questionnaires were sent to analyze their clinical and neuroimaging profiles. Results Among a total of 109 patients registered to the national surveillance, 10 (9%) were less than age 15 years. The annual incidence rate of childhood-onset JE was higher during 2005–15 than that during 1995–2004 (4.3 × 10–3 vs 1.1 × 10–3 per 100000, respectively; P =.04). Endemic regions overlapped with prefectures that farmed pigs harboring antibodies against JE virus with high prevalence. Detailed clinical data were collected from 9 patients. None of them died, but 5 of 9 patients (56%) had neurological sequelae after recovery. One patient who was partially vaccinated with 2 doses of JE vaccine fully recovered from a coma. The age of 3 years or less was associated with unfavorable neurological prognosis. Conclusions Our data provide evidence for the importance and prophylactic effect of the JE vaccine in young children in the endemic area. [ABSTRACT FROM AUTHOR]

Background: The immune responses to pneumococcal conjugate vaccine (PCV) are low in immunocompromised hosts. The effect of memory B cells on the immune response to PCV remains elusive.Methods: In this prospective study, 53 children who received 7-valent PCV were enrolled. Antipneumococcal immunoglobulin G (IgG) levels and opsonization index (OI) titers, along with lymphocyte subsets, were investigated in immunocompromised and immunocompetent hosts. Immunocompromised patients comprised 8 hematopoietic stem cell transplant recipients (group A) and 9 immunosuppressive therapy recipients (group B), and controls consisted of 14 children aged >1 year (group C) and 22 infants (group D).Results: Serotype-specific IgG concentrations and OIs in group A were lower than those in group C. These did not differ among groups B, C, and D. The rates of achieving immunity (defined as an IgG level of 1.0 µg/mL and an OI of 8) in group A were also lower than in group C. Despite the sustained numbers of total T cells and B cells, CD27(+) B-cell and CD4(+) T-cell counts in group A were lower than those in group C. In group B, the immunoglobulin D-expressing CD27(-) B-cell count was only lower than that in group C.Conclusions: Circulating numbers of CD27(+) B cells, rather than CD4(+) T cells, may predict the effective PCV responses in immunocompromised children. [ABSTRACT FROM AUTHOR]

Abstract Background There is limited information available regarding the role of infliximab (IFX) following the acute phase of Kawasaki disease (KD). We aimed to evaluate whether IFX is associated with coronary artery aneurysm (CAA) regression. Methods Between 2005 and 2016, we identified 971 consecutive patients with KD from 3 tertiary institutions, and 49 (5%) with CAAs were enrolled in our study. Patients were divided into 2 groups: 27 who received IFX and 22 who did not. The persistence rate of CAAs was compared between the groups. Results Age, sex, and duration of the febrile period did not significantly differ between the groups. The maximum value of C-reactive protein was higher in the IFX- than in the non-IFX group. The maximum z-score of CAAs did not differ between the groups. The 2-, 4- and 6-year cumulative persistence rate of CAA was 24%, 24% and 24% in IFX-group, whereas 67%, 52% and 33% in non-IFX group, respectively (P = 0.03). The median duration of CAA regression was 1.1 vs. 4.6 years. Among those who developed medium- or large-sized CAAs, the 2-, 4- and 6-year cumulative persistence rate of CAA was 33%, 33% and 33% in IFX group, whereas 77%, 51% and 48% in non-IFX group, respectively (P = 0.047). Multivariate logistic regression analysis indicated that the maximum z-score (hazard ratio 0.72, p < 0.001) and response to IFX (hazard ratio 4.56, p = 0.017) were independently related to regression. Conclusion IFX therapy was observed to be effective for the early improvement of CAAs in patients with intravenous immunoglobulin-resistant KD. Highlights • Infliximab is effective for the early coronary artery regression in Kawasaki disease. • Infliximab reduce persistence rate of coronary artery aneurysm in convalescent phase. • Infliximab may improve the long-term prognosis of Kawasaki disease. [ABSTRACT FROM AUTHOR]