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Competing Interests: Takashi Nitta is a consultant for AtriCure. Michael Yii is a consultant for AtriCure as a proctor. Mark La Meir is a consultant for AtriCure. Christoph T Starck declares payment to his institution related to his activity as speaker fees, honoraria, consultancy, advisory board fees, investigator, committee member from AngioDynamics, Abiomed, AtriCure, Medtronic, Spectranetics, Biotronik, Liva Nova (Sorin) and Cook Medical and departmental or institutional research funding from Cook Medical, Hylomorph.

Objectives: The study aimed to compare the immunogenicity and safety of fractional (half) third doses of heterologous COVID-19 vaccines (AZD1222 or BNT162b2) to full doses after the two-dose CoronaVac and when boosting after three different extended intervals., Methods: At 60-<90, 90-<120, or 120-180 days intervals after the two-dose CoronaVac, participants were randomized to full-dose or half-dose AZD1222 or BNT162b2, followed up at day 28, 60, and 90. Vaccination-induced immune responses to Ancestral, Delta, and Omicron BA.1 strains were evaluated by antispike, pseudovirus, and microneutralization and T cell assays. Descriptive statistics and noninferiority cut-offs were reported as geometric mean concentration or titer and concentration or titer ratios comparing baseline to day 28 and day 90 and different intervals., Results: No safety concerns were detected. All assays and intervals showed noninferior immunogenicity between full doses and half doses. However, full-dose vaccines and/or longer 120-180-day intervals substantially improved the immunogenicity (measured by antispike or measured by pseudotyped virus neutralizing titers 50; P <0.001). Seroconversion rates were over 90% against the SARS-CoV-2 strains by all assays. Immunogenicity waned more quickly with half doses than full doses but remained high against the Ancestral or Delta strains. Against Omicron, the day 28 immunogenicity increased with longer intervals than shorter intervals for full-dose vaccines., Conclusion: Immune responses after day 28 when boosting at longer intervals after the two-dose CoronaVac was optimal. Half doses met the noninferiority criteria compared with the full dose by all the immune assays assessed., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Mammalian hosts often develop distinct immune response against the diverse parasitic helminths that have evolved for immune evasion. Interleukin-25 (IL-25), an IL-17 cytokine family member, plays a key role in initiating the protective immunity against several parasitic helminths; however, the involvement and underlying mechanisms by which IL-25 mediates immune response against Trichinella spiralis infection have not been investigated. Here we showed that IL-25 functions in promoting protective immunity against T. spiralis infection. Mice treated with IL-25 exhibited a lower worm burden and fewer muscle larvae in the later stage of T. spiralis infection. In contrast, mice treated with neutralizing antibody against IL-25 failed to expel T. spiralis effectively. During T. spiralis infection, intestinal IL-25 expression was rapidly elevated before the onset of IL-4 and IL-9 induction. While antigen-specific Th2 and Th9 immune responses were both developed during T. spiralis infection, an antigen-specific Th9 response appeared to be transiently induced in the early stage of infection. Mice into which antigen-specific T cells deficient in IL-9 were transferred were less effective in worm clearance than those given wild-type T cells. The strength of the antigen-specific Th9 immune response against T. spiralis could be enhanced or attenuated after treatment with IL-25 or neutralizing antibody against IL-25, respectively, correlating positively with the levels of intestinal mastocytosis and the expression of IL-9-regulated genes, including mast cell- and Paneth cell-specific genes. Thus, our study demonstrates that intestinal IL-25 promotes protective immunity against T. spiralis infection by inducing antigen-specific Th9 immune response.

Pyrimethamine-sulfadoxine (PS) is used as a second-line treatment for P. falciparum malaria patients who fail to respond to chloroquine. Resistance to these drugs has been shown to encode with point mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) genes. Our aim was to assess the comparative rate of point mutation occurring in DHFR and DHPS genes among P. falciparum isolates from India and Thailand where the use of PS is at a different rate. We used the mutation-specific polymerase chain reaction (PCR) technique and mutation-specific restriction digestion to determine the prevalence of DHFR and DHPS gene mutations at codons 16, 51, 59, 108, 164 and at 436, 437, 581 and 613, respectively. In the 89 clinical isolates from India, in the case of the DHFR gene, we found 71 of S108N, 10 of N51I, 28 of C59R and four of I164L types. Among the 50 isolates from Thailand the rate of point mutations in the DHFR gene was higher at four codon positions. We found 47 of S108N, 18 of N51I, 23 of C59R and 12 of I164L types. None of the isolates from either country possessed the paired mutations S108T and A16V. Mutations of the DHPS gene were less frequent among the Indian isolates: 4.5% showed DHPS gene mutation, two of S436F, A437G, A613T and two of S436F, A613T; whereas 66% (33/50) of the Thai isolates had mutated at codons 436, 437, 581 and 613 which include 13 of S436F, 15 of A437G, 19 of A581G and 25 of A613S/T, ranging from single to quadruple mutant types. Among the Indian isolates, DHFR point mutations were very frequent and 85/89 had a wild type DHPS genetic profile. The pattern of mutations in the samples from Thailand was different, as most were associated with point mutations in DHFR and DHPS genes.

We previously reported monoclonal antibodies (MAbs) specific to S. typhi 52 kDa antigen which do not cross react with related protein antigens from 11 bacteria causing enteric fever and enteric fever-like illness. Using the combination of these specific MAbs and recombinant DNA technology, expression plasmids containing the antigen gene producing substantial amount of the S. typhi protein antigen have been established. Plasmid pSKM-T7 containing the specific 52 kDa antigen gene was cloned and the antigen expressed was detectable by immunoblotting using specific mAbs. The complete nucleotide sequence of this gene was compared with other bacterial sequences and found to be highly homologous with the flagellin gene H1-d of S. muenchen except in the hypervariable region in the central portion. The specific 52 kDa antigen of S. typhi detected by our MAbs is thus a flagellin.