Search

Studies of antenatal women form the predominant source of data on HIV-1 prevalence in Africa. Identifying factors associated with prevalent HIV is important in targeting diagnostic services and care. Between November 1997 and January 2000, 14,110 postnatal women from Harare, Zimbabwe were tested by ELISAs reactive to both HIV-1 and HIV-2; a subset of positive samples was confirmed with assays specific for HIV-1 and HIV-2. Baseline characteristics were elicited and modelled to identify risk factors for prevalent HIV infection. HIV-1 and HIV-2 prevalences were 32.0% (95% CI 31.2-32.8) and 1.3% (95% CI 1.1-1.5), respectively; 4% of HIV-1-positive and 99% of HIV-2-positive women were co-infected. HIV-1 prevalence increased from 0% among 14-year-olds to >45% among women aged 29-31 years, then fell to <20% among those aged>40 years. In multivariate analyses, prevalence increased with parity, was lower in married women than in single women, divorcees and widows, and higher in women with the lowest incomes and those professing no religion. Adjusted HIV-1 prevalence increased during 1998 and decreased during 1999. Age modified the effects of parity, home ownership and parental education. Among older women, prevalence was greater for women who were not homeowners. Among younger women, prevalence increased with parity and low parental education. None of these factors distinguished women co-infected with HIV-2 from those infected with HIV-1 alone. Prevalent HIV-1 infection is associated with financial insecurity and weak psychosocial support. The ZVITAMBO study apparently spanned the peak of the HIV-1 epidemic among reproductive women in Harare. [ABSTRACT FROM AUTHOR]

BACKGROUND: Low maternal serum retinol level is a risk factor for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality. The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency; neonatal dosing is under consideration. We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT, HIV-free survival, and mortality in HIV-exposed infants. METHODS: A total of 14,110 mother-infant pairs were enrolled < or =96 h after delivery, and both mother and infant, mother only, infant only, or neither received vitamin A supplementation in a randomized, placebo-controlled trial with a 2 x 2 factorial design. All but 4 mothers initiated breast-feeding. A total of 4495 infants born to HIV-positive women were included in the present analysis. RESULTS: Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months. However, the timing of infant HIV infection modified the effect that supplementation had on mortality. Vitamin A supplementation had no effect in infants who were polymerase chain reaction (PCR) negative for HIV at baseline. In infants who were PCR negative at baseline and PCR positive at 6 weeks, neonatal supplementation reduced mortality by 28% (P=.01), but maternal supplementation had no effect. In infants who were PCR negative at 6 weeks, all 3 vitamin A regimens were associated with 2-fold higher mortality (P< or =.05). CONCLUSIONS: Targeted vitamin A supplementation of HIV-positive children prolongs their survival. However, postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks. These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA)-E and HLA-G molecules act as powerful modulators of the innate immune response. The present study shows that the HLA-E(G) genetic variant (the HLA-E*0103 allele) alone is significantly (P = .001) associated with a 4.0-fold decreased risk of human immunodeficiency virus 1 (HIV-1) infection in Zimbabwean women. Furthermore, women carrying the combination of the protective HLA-E(G) homozygote and HLA-G*0105N heterozygote genotypes had a 12.5-fold decreased risk of HIV-1 infection (P = .03), compared with women carrying neither genotype. These associations remained significant after adjustment was made for other significant sociodemographic risk factors for HIV prevalence in this population. In conclusion, HLA-E and HLA-G polymorphisms can independently and synergistically influence susceptibility to heterosexual acquisition of HIV-1. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

BACKGROUND: Young infants are at risk of vitamin A deficiency. Supplementation of breastfeeding mothers improves the vitamin A status of their infants, but there are no data regarding its effect on infant mortality, and data on the effect of directly supplementing infants during the first few weeks of life are conflicting. OBJECTIVE: The objective was to measure the effect on infant mortality of supplementing neonates and their HIV-negative mothers with single, large doses of vitamin A during the immediate postpartum period. DESIGN: A randomized, placebo-controlled, 2-by-2 factorial design trial was conducted in 14,110 mothers and their infants; 9208 of the mothers were HIV-negative at delivery, remained such during the postpartum year, and were retained in the current analysis. The infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A (Aa), mothers received vitamin A and infants received placebo (Ap), mothers received placebo and infants received vitamin A (Pa), and both mothers and infants received placebo (Pp). The vitamin A dose in the mothers was 400,000 IU and in the infants was 50,000 IU. The mother-infant pairs were followed to 12 mo. RESULTS: Hazard ratios (95% CI) for 12 mo mortality among infants in the maternal-supplemented and infant-supplemented groups were 1.17 (0.87, 1.58) and 1.08 (0.80, 1.46), respectively. Hazard ratios (95% CI) for the Aa, Ap, and Pa groups compared with the Pp group were 1.28 (0.83, 1.98), 1.27 (0.82, 1.97), and 1.18 (0.76, 1.83), respectively. These data indicate no overall effect. Serum retinol concentrations among a subsample of women were similar to reference norms. CONCLUSION: Postpartum maternal or neonatal vitamin A supplementation may not reduce infant mortality in infants of HIV-negative women Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Background: Travel to hepatitis A-endemic countries is frequent among North Americans. Such travel carries significant risks for the individuals themselves and for the general population. We documented the patterns of use of travel clinics in a large Canadian adult population.Methods: Travelers who had visited a hepatitis A-endemic country between 1990 and the time of the survey in 1999 were eligible. Subjects were identified from a representative sample of 4,002 adults from the two largest Canadian provinces. They were contacted by random digit dialing and interviewed by telephone.Results: Only 15% of trips had been preceded by a visit to a travel clinic. The probability of visiting a travel clinic was approximately 10 times greater for travelers considered to be in the high-risk category than for those in the low-risk category, but the former represented only 2% of the total. The probability of visiting a travel clinic was approximately 23 times greater for travelers who were aware of the health risks in their country of destination. Income level was not associated with attendance at a travel clinic, and cost was rarely mentioned as a reason for not attending such a travel clinic before departure.Conclusions: Each year, millions of Canadian travelers go to hepatitis A-endemic countries without consulting a travel clinic. Active steps must be taken by public health authorities to improve their utilization of health services and prevent the accrued health risk for these travelers. [ABSTRACT FROM AUTHOR]

Background: Increases in travel-related illness require new partnerships to ensure travelers are prepared for health risks abroad. The travel agent is one such partner and efforts to encourage travel agents to refer at-risk travelers to travel health clinics may help in reducing travel-attributable morbidity.Methods: A health promotion intervention encouraging travel agents to refer at-risk travelers to travel health clinics was evaluated. Information on the knowledge, attitudes, and behaviors of travel agents before and after the intervention was compared using two self-administered questionnaires. The Wilcoxon signed rank test was used to compare the mean difference in overall scores to evaluate the overall impact of the intervention and also subscores for each of the behavioral construct groupings (attitudes, barriers, intent, and subjective norms). Multiple regression techniques were used to evaluate which travel agent characteristics were independently associated with a stronger effect of the intervention.Results: A small improvement in travel agents overall attitudes and beliefs (p =.03) was found, in particular their intention to refer (p =.01). Sixty-five percent of travel agents self-reported an increase in referral behavior; owners or managers of the agency were significantly more likely to do so than other travel agents (OR = 7.25; 95% CI: 1.64 32.06). Older travel agents, those that worked longer hours and those with some past referral experience, had significantly higher post-intervention scores.Conclusions: Travel agents can be willing partners in referral, and agencies should be encouraged to develop specific referral policies. Future research may be directed toward investigating the role of health education in certification curricula, the effectiveness of different types of health promotion interventions, including Internet-facilitated interventions, and the direct impact that such interventions would have on travelers attending travel health clinics. [ABSTRACT FROM AUTHOR]

Measles antigen-specific immune responses were evaluated 1 and 6 months after revaccination in 60 previously vaccinated subjects (9.4 +/- 3.4 years of age) who had either undetectable or low plaque reduction neutralization (PRN) titers (< 200). PRN titers were increased in all subjects at 1 month (590 +/- 61; range, 129-2513) but fell again in 66% of subjects by 6 months (214 +/- 29; range, 30-794). At 6 months, 23 (38%) had subprotective (< 120) or borderline (< 200) PRN titers. Lymphoproliferative responses to measles virus antigens were low overall before revaccination (mean stimulation index [SI], 2.6 +/- 0.4; range, 0.5-13.5) but were readily detectable at 1 (SI, 145.8 +/- 2.6; range, 1.4-80) and 6 months after revaccination (SI, 9.4 +/- 1.8; range, 1.1-87). Before revaccination, 10 of the subjects (50%) with low positive PRN titers had SIs > or = 3. At 6 months after revaccination, 18 subjects (78%) with PRN titers < or = 200 had SIs > or = 3. These data suggest that cellular responses to measles virus may be better sustained than antibody titers after vaccination and revaccination in some subjects. [ABSTRACT FROM AUTHOR]

The poem "Compassion" by BJ Ward is presented. First Line: Out in this profane city, Last Line: to make music.

The poem "Building Codes" by BJ Ward is presented. First Line: Dear Tony, Last Line: that meets all state regulations.

Presents the poem "17 Becomes 43," by BJ Ward. First Line: Whatever happened to Hills Diner? Last Line: and is her beehive still towering?

Background: Hemagglutinin (HA)-inhibiting antibodies contribute to the immune defense against influenza infection. However, there are insufficient data on the extent of correlation between vaccine-elicited HA antibodies and protection in children against different influenza strains, particularly when comparing live attenuated influenza vaccines (LAIV) versus inactivated influenza vaccines (IIV)., Methods: We measured postvaccination hemagglutination-inhibition (HAI) titers in 3-15-year-old participants of a cluster-randomized controlled trial of trivalent LAIV(3) versus IIV(3) in Canadian Hutterite colonies. We assessed HAI titers as predictors of symptomatic, reverse transcription polymerase chain reaction (RT-PCR)-confirmed influenza over 3 influenza seasons using Cox proportional hazards regression models with vaccine type as a covariate., Results: For each log2 unit increase in postvaccination HAI against A/H1N1 in 2013-2014, A/H3N2 2014-2015, and B/Yamagata in 2013-2014 (each the predominant circulating strain for the respective influenza season), the reduction in the risk of confirmed influenza was equal to 29.6% (95% confidence interval [CI], 17.1%-39.5%), 34.8% (95% CI, 17.2%-47.9%), and 31.8% (95% CI, 23.8%-38.5%), respectively. No reduction in the risk of influenza was observed with B/Yamagata-specific HAI titers in 2012-2013, which was dominated by a mixture of Yamagata and Victoria strains. Despite the overall lower HAI titers in the LAIV3 group, both H1N1 and H3N2 HAI titers were associated with protection against subtype matched influenza., Conclusions: Both LAIV3- and IIV3-elicited HA antibodies are associated with protection against influenza infection in seasons when the vaccine strains match the circulating influenza strain subtypes, supporting the use of HAI as a correlate of protection for both vaccine types in children., Competing Interests: Potential conflicts of interest. M. S. M. has received honoraria from Seqirus, Sanofi, and Grifols; research funding from Providence Therapeutics and Pfizer; and is cofounder of Aeroimmune, Inc. M. L. reports funding from World Health Organization, Medical Research Council UK, and CIHR; advisory board membership for GSK, Pfizer, Medicago, Merk, Seqirus, Sanofi, and Novavax; and data safety monitoring committee membership for CanSino Biologics and PATH. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: The incidence of varicella in Canada has decreased by almost 99% since vaccination was introduced. However, variation in the timing and eligibility of vaccination programs across the country has resulted in some cohorts being under-vaccinated and therefore potentially susceptible to infection., Methods: We used nationally representative specimens from the Biobank of Statistics Canada's Canadian Health Measures Survey (CHMS) as well as residual specimens from Ontario collected between 2009-2014 to estimate population immunity across age-groups and geography, and identify any groups at increased risk of varicella infection., Results: The weighted proportion of specimens with antibody levels above the threshold of protection was 93.6% (95% CI: 92.4, 95.0). Protection was lowest among those aged 3-5 years (54.3%; 95% CI: 47.3, 61.4), but increased with age. Individuals born outside Canada had more than twice the odds of varicella susceptibility than those born in Canada (aOR: 2.7; 95% CI: 1.4, 5.0; p = 0.004). There were no differences by sex or geography within Canada, and there were no statistically significant differences when Ontario CHMS sera were compared to Ontario residual sera, apart from in participants aged 12-19 year age-group, for whom the CHMS estimate (91.2%; 95% CI: 86.7, 95.7) was significantly higher (p = 0.03) than that from residual specimens (85.9%, 95% CI: 81.1, 90.8)., Discussion: Varicella immunity in Canada is changing. Children appear to have low population immunity, placing them at greater risk of infection and at increased risk of severe disease as they age. Our results underscore the importance of performing periodic serosurveys to monitor further population immunity changes as the proportion of vaccine-eligible birth-cohorts increases, and to continually assess the risk of outbreaks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wright et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). CoVLP+AS03 enhanced the magnitude and durability of circulating antibodies and antigen-specific CD4 + T cell and memory B cell responses. Antigen-specific CD4 + T cells in the CoVLP+AS03 group at day 42 correlated with antigen-specific memory B cells at 6 months. CoVLP+AS03 induced memory B cell responses, which accumulated somatic hypermutations over 6 months, resulting in enhanced neutralization breadth of monoclonal antibodies. Furthermore, the fraction of broadly neutralizing antibodies encoded by memory B cells increased between day 42 and 6 months. These results indicate that AS03 enhances the antigenic breadth of B cell memory at the clonal level and induces progressive maturation of the B cell response.

Developing a vaccine against Clostridioides difficile is a key strategy to protect the elderly. Two candidate vaccines using a traditional approach of intramuscular (IM) delivery of recombinant antigens targeting C. difficile toxins A (TcdA) and B (TcdB) failed to meet their primary endpoints in large phase 3 trials. To elicit a mucosal response against C. difficile , we repurposed an attenuated strain of Salmonella Typhimurium (YS1646) to deliver the receptor binding domains (rbd) of TcdA and TcdB to the gut-associated lymphoid tissues, to elicit a mucosal response against C. difficile . In this study, YS1646 candidates with either rbdA or rbdB expression cassettes integrated into the bacterial chromosome at the att Tn 7 site were generated and used in a short-course multimodal vaccination strategy that combined oral delivery of the YS1646 candidate(s) on days 0, 2, and 4 and IM delivery of recombinant antigen(s) on day 0. Five weeks after vaccination, mice had high serum IgG titers and increased intestinal antigen-specific IgA titers. Multimodal vaccination increased the IgG avidity compared to the IM-only control. In the mesenteric lymph nodes, we observed increased IL-5 secretion and increased IgA + plasma cells. Oral vaccination skewed the IgG response toward IgG2c dominance (vs IgG1 dominance in the IM-only group). Both oral alone and multimodal vaccination against TcdA protected mice from lethal C. difficile challenge (100% survival vs 30% in controls). Given the established safety profile of YS1646, we hope to move this vaccine candidate forward into a phase I clinical trial.IMPORTANCE Clostridioides difficile remains a major public health threat, and new approaches are needed to develop an effective vaccine. To date, the industry has focused on intramuscular vaccination targeting the C. difficile toxins. Multiple disappointing results in phase III trials have largely confirmed that this may not be the best strategy. As C. difficile is a pathogen that remains in the intestine, we believe that targeting mucosal immune responses in the gut will be a more successful strategy. We have repurposed a highly attenuated Salmonella Typhimurium (YS1646), originally pursued as a cancer therapeutic, as a vaccine vector. Using a multimodal vaccination strategy (both recombinant protein delivered intramuscularly and YS1646 expressing antigen delivered orally), we elicited both systemic and local immune responses. Oral vaccination alone completely protected mice from lethal challenge. Given the established safety profile of YS1646, we hope to move these vaccine candidates forward into a phase I clinical trial., Competing Interests: K.W. and B.J.W. are inventors on a patent for YS1646 as a vaccine against Clostridioides difficile held by Aviex Technologies LLC. S.H. and C.M.D. have no conflict of interest to declare.

Importance: Despite widespread use, summary evidence from prior meta-analyses has contradictory conclusions regarding whether oseltamivir decreases the risk of hospitalization when given to outpatients. Several large investigator-initiated randomized clinical trials have not yet been meta-analyzed., Objective: To assess the efficacy and safety of oseltamivir in preventing hospitalization among influenza-infected adult and adolescent outpatients., Data Sources: PubMed, Ovid MEDLINE, Embase, Europe PubMed Central, Web of Science, Cochrane Central, ClinicalTrials.gov, and WHO International Clinical Trials Registry were searched from inception to January 4, 2022., Study Selection: Included studies were randomized clinical trials comparing oseltamivir vs placebo or nonactive controls in outpatients with confirmed influenza infection., Data Extraction and Synthesis: In this systematic review and meta-analysis, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Two independent reviewers (R.H. and É.B.C.) extracted data and assessed risk of bias using the Cochrane Risk of Bias Tool 2.0. Each effect size was pooled using a restricted maximum likelihood random effects model. The quality of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework., Main Outcomes and Measures: Hospitalization was pooled as risk ratio (RR) and risk difference (RD) estimates with 95% CIs., Results: Of 2352 studies identified, 15 were included. The intention-to-treat infected (ITTi) population was comprised of 6166 individuals with 54.7% prescribed oseltamivir. Across study populations, 53.9% (5610 of 10 471) were female and the mean age was 45.3 (14.5) years. Overall, oseltamivir was not associated with reduced risk of hospitalization within the ITTi population (RR, 0.79; 95% CI, 0.48 to 1.29; RD, -0.17%; 95% CI, -0.23% to 0.48%). Oseltamivir was also not associated with reduced hospitalization in older populations (mean age ≥65 years: RR, 1.01; 95% CI, 0.21 to 4.90) or in patients considered at greater risk of hospitalization (RR, 0.65; 0.33 to 1.28). Within the safety population, oseltamivir was associated with increased nausea (RR, 1.43; 95% CI, 1.13 to 1.82) and vomiting (RR, 1.83; 95% CI, 1.28 to 2.63) but not serious adverse events (RR, 0.71; 95% CI, 0.46 to1.08)., Conclusions and Relevance: In this systematic review and meta-analysis among influenza-infected outpatients, oseltamivir was not associated with a reduced risk of hospitalization but was associated with increased gastrointestinal adverse events. To justify continued use for this purpose, an adequately powered trial in a suitably high-risk population is justified.

Background: Norovirus (NoV) is the most common cause of diarrheal episodes globally. Issues with in vitro cultivation systems, genetic variation, and animal models have hindered vaccine development. Plant-derived virus-like particles (VLPs) may address some of these concerns because they are highly immunogenic, can be administered by different routes, and can be rapidly produced to accommodate emerging viral strains., Methods: NoV VLPs (NoVLP) composed of the surface viral protein (VP) 1 of the GI and GII genogroups were produced in Nicotiana benthamiana using an Agrobacterium tumefaciens-based recombinant transient expression system. Leaves from infiltrated plants were harvested and NoVLPs were extracted and purified. The safety and immunogenicity of the GII.4 NoVLP, the genotype currently causing most human disease, were subsequently examined in rabbits and mice., Results: Fifteen GI and GII NoVLPs were successfully expressed in N. benthamiana and were structurally similar to NoV virions, as determined by cryogenic transmission electron microscopy. The NoVLP was well-tolerated, with no local or systemic signs of toxicity in rabbits. Three intramuscular doses of the GII.4 NoVLP adjuvanted with aluminum hydroxide induced robust IgG titers, IgG-secreting cells, histo-blood group antigen blocking titers, and IFNγ-secreting T cells in mice. In addition to circulating antibodies, oral administration of the NoVLP in mice induced significant IgA levels in feces, indicative of a mucosal response., Conclusions: The plant-made NoVLP vaccine was safe and immunogenic in mice and rabbits. Multi-modal vaccination, combining oral and intramuscular administration could be considered for future clinical development to maximize systemic and mucosal immune responses., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GA, DB, MAD, BJW, MMC, MD, POL, SP, and ST are employees of Medicago Inc. JS is employee of the Center for Vaccine Preventable Diseases, Dalla Lana School of Public Health, University of Toronto, ON, Canada, where she is supported by a postdoctoral fellowship from the Canadian Immunization Research Network. HH is employee of Research Institute of the McGill University Health Centre (under MITACS Elevate post-doctorate fellowship), Montreal, QC, Canada. MB and CD are employees of Providence Therapeutics. NL is employee of PharmaJet, CO, USA., (Copyright © 2023. Published by Elsevier Ltd.)

Schistosomiasis threatens hundreds of millions of people worldwide. The larval stage of Schistosoma mansoni migrates through the lung and adult worms reside adjacent to the colonic mucosa. Several candidate vaccines are in preclinical development, but none is designed to elicit both systemic and mucosal responses. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to express Cathepsin B (CatB), a digestive enzyme important for the juvenile and adult stages of the S. mansoni life cycle. Previous studies have demonstrated the prophylactic and therapeutic efficacy of our plasmid-based vaccine. Here, we have generated chromosomally integrated (CI) YS1646 strains that express CatB to produce a viable candidate vaccine for eventual human use (stability, no antibiotic resistance). 6-8-week-old C57BL/6 mice were vaccinated in a multimodal oral (PO) and intramuscular (IM) regimen, and then sacrificed 3 weeks later. The PO + IM group had significantly higher anti-CatB IgG titers with greater avidity and mounted significant intestinal anti-CatB IgA responses compared to PBS control mice (all P < 0.0001). Multimodal vaccination generated balanced T H 1/T H 2 humoral and cellular immune responses. Production of IFNγ by both CD4 + and CD8 + T cells was confirmed by flow cytometry (P < 0.0001 & P < 0.01). Multimodal vaccination reduced worm burden by 80.4%, hepatic egg counts by 75.2%, and intestinal egg burden by 78.4% (all P < 0.0001). A stable and safe vaccine that has both prophylactic and therapeutic activity would be ideal for use in conjunction with praziquantel mass treatment campaigns., (© 2023. The Author(s).)

Despite the success of existing COVID-19 vaccine platforms, the persistent limitations in global deployment of vaccines and waning immunity exhibited by many of the currently deployed vaccine platforms have led to perpetual outbreaks of SARS-CoV-2 variants of concern. Thus, there is an urgent need to develop new durable vaccine candidates, to expand the global vaccine pipeline, and provide safe and effective solutions for every country worldwide. Here we deeply profiled the functional humoral response induced by two doses of AS03-adjuvanted and non-adjuvanted plant-derived Coronavirus-like particle (CoVLP) vaccine candidate from the phase 1 clinical trial, at peak immunogenicity and six months post-vaccination. AS03-adjuvanted CoVLP induced robust and durable SARS-CoV-2 specific humoral immunity, marked by strong IgG1antibody responses, potent FcγR binding, and antibody effector function. Contrary to a decline in neutralizing antibody titers, the FcγR2A-receptor binding capacity and antibody-mediated effector functions, such as opsonophagocytosis, remained readily detectable for at least six months., (© 2023. The Author(s).)

Poor and unpredictable dewatering performance of fecal sludge is a major barrier to sanitation provision in urban areas not served by sewers. Fecal sludge comprises everything that accumulates in onsite containments, and its characteristics are distinct from wastewater sludges and from feces. There is little fundamental understanding of what causes poor dewatering in fecal sludge. For the first time, we demonstrate that particle size distribution is a driver of dewatering performance in fecal sludge, and is associated with level of stabilization. Higher concentrations of small particles (<10 μm) and smaller median aggregate size (D50) corresponded to poor dewatering performance (measured by capillary suction time (CST) and supernatant turbidity) in field samples from Kenya and Uganda and in controlled laboratory anaerobic storage experiments. More stabilized fecal sludge (higher C/N, lower VSS/TSS) had better dewatering performance, corresponding to lower concentrations of small particles. Samples with the largest aggregates (D50 > 90 μm) had higher abundance of Gammaproteobacteria Pseudomonas, and samples with the smallest aggregates (D50 ≤ 50 μm) were characterized by higher abundance of Bacteroidetes Vadin HA17 and Rikenellaceae. Contrary to common perceptions, stabilization, particle size distribution, and dewatering performance were not dependent on time intervals between emptying of onsite containments or on time in controlled anaerobic storage experiments. Our results suggest that the stabilization process in onsite containments, and hence the dewaterability of sludge arriving at treatment facilities, is not dependent on time in containment but is more likely associated with specific microbial populations and the in-situ environmental conditions which promote or discourage their growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

As the SARS-CoV-2 pandemic evolves, vaccine evaluation needs to include consideration of both durability and cross-reactivity. This report expands on previously reported results from a Phase 1 trial of an AS03-adjuvanted, plant-based coronavirus-like particle (CoVLP) displaying the spike (S) glycoprotein of the ancestral SARS-CoV-2 virus in healthy adults (NCT04450004). Humoral and cellular responses against the ancestral strain were evaluated 6 months post-second dose (D201) as secondary outcomes. Independent of dose, all vaccinated individuals retain binding antibodies, and ~95% retain neutralizing antibodies (NAb). Interferon gamma and interleukin-4 responses remain detectable in ~94% and ~92% of vaccinees respectively. In post-hoc analyses, variant-specific (Alpha, Beta, Delta, Gamma and Omicron) NAb were assessed at D42 and D201. Using a live virus neutralization assay, broad cross-reactivity is detectable against all variants at D42. At D201, cross-reactive antibodies are detectable in almost all participants against Alpha, Gamma and Delta variants (94%) and the Beta variant (83%) and in a smaller proportion against Omicron (44%). Results are similar with the pseudovirion assay. These data suggest that two doses of 3.75 µg CoVLP+AS03 elicit a durable and cross-reactive response that persists for at least 6 months post-vaccination., (© 2022. The Author(s).)

The rapid spread of SARS-CoV-2 continues to impact humanity on a global scale with rising total morbidity and mortality. Despite the development of several effective vaccines, new products are needed to supply ongoing demand and to fight variants. We report herein a pre-specified interim analysis of the phase 2 portion of a Phase 2/3, randomized, placebo-controlled trial of a coronavirus virus-like particle (CoVLP) vaccine candidate, produced in plants that displays the SARS-CoV-2 spike glycoprotein, adjuvanted with AS03 (NCT04636697). A total of 753 participants were recruited between 25th November 2020 and 24th March 2021 into three groups: Healthy Adults (18-64 years: N = 306), Older Adults (≥65 years: N = 282) and Adults with Comorbidities (≥18 years: N = 165) and randomized 5:1 to receive two intramuscular doses of either vaccine (3.75 µg CoVLP/dose+AS03) or placebo, 21 days apart. This report presents safety, tolerability and immunogenicity data up to 6 months post-vaccination. The immune outcomes presented include neutralizing antibody (NAb) titres as measured by pseudovirion assay at days 21 and 42 as well as neutralizing antibody cross-reactivity to several variants of concern (VOCs): Alpha, Beta, Gamma, Delta, and Omicron (BA.1), up to 201 days post-immunization. Cellular (IFN-γ and IL-4 ELISpot) response data in day 21 and 42 peripheral blood are also presented. In this study, CoVLP+AS03 was well-tolerated and adverse events (AE) after each dose were generally mild to moderate and transient. Solicited AEs in Older Adults and Adults with Comorbidities were generally less frequent than in Healthy Adults and the reactogenicity was higher after the second dose. CoVLP+AS03 induced seroconversion in &gt;35% of participants in each group after the first dose and in ~98% of participants, 21 days after the second dose. In all cohorts, 21-days after the second dose, NAb levels in sera against the vaccine strain were ~10-times those in a panel of convalescent sera. Cross-reactivity to Alpha, Beta and Delta variants was generally retained to day 201 (&gt;80%) while cross-reactivity to the Gamma variant was reduced but still substantial at day 201 (73%). Cross-reactivity to the Omicron variant fell from 72% at day 42 to 20% at day 201. Almost all participants in all groups (&gt;88%) had detectable cellular responses (IFN-γ, IL-4 or both) at 21 days after the second dose. A Th1-biased response was most evident after the first dose and was still present after the second dose. These data demonstrated that CoVLP+AS03 is well-tolerated and highly immunogenic, generating a durable (at least 6 months) immune response against different VOCs, in adults ≥18 years of age, with and without comorbidities., (© 2022. The Author(s).)

We assessed the frequency and correlates of COVID-19 vaccine hesitancy before Canada's vaccine rollout. A cross-sectional vaccine hesitancy survey was completed by consecutive patients/family members/staff who received the influenza vaccine at McGill University affiliated hospitals. Based on the self-reported likelihood of receiving a future vaccine (scale 0-10), the following three groups were defined: non-hesitant (score 10), mildly hesitant (7.1-9.9), and significantly hesitant (0-7). Factors associated with vaccine hesitancy were assessed with multivariate logistic regression analyses and binomial logistic regression machine learning modelling. The survey was completed by 1793 people. Thirty-seven percent of participants (n = 669) were hesitant (mildly: 315 (17.6%); significantly: 354 (19.7%)). Lower education levels, opposition and uncertainty about vaccines being mandatory, feelings of not receiving enough information about COVID-19 prevention, perceived social pressure to get a future vaccine, vaccine safety concerns, uncertainty regarding the vaccine risk-benefit ratio, and distrust towards pharmaceutical companies were factors associated with vaccine hesitancy. Vaccine safety concerns and opposition to mandatory vaccinations were the strongest correlates of vaccine hesitancy in both the logistic regressions and the machine learning model. In conclusion, in this study, over a third of people immunized for influenza before the COVID-19 vaccine rollout expressed some degree of vaccine hesitancy. Effectively addressing COVID-19 vaccine safety concerns may enhance vaccine uptake.

As the importance of fecal sludge management (FSM) is increasingly being realized, the need for adequately designed and functioning fecal sludge (FS) treatment plants is also increasing. Research to fill this gap is only emerging and dewatering is a key challenge for developing sustainable treatment solutions. This study evaluated the effect of extracellular polymeric substances (EPS) on dewaterability of FS, and how EPS and dewaterability change during anaerobic storage (as a proxy for time in onsite containment). EPS was extracted from FS and activated sludge using Na 2 CO 3 and sonication and added to sludge samples to determine the effect on dewaterability. The results confirmed that an increase in EPS had a direct impact of decreasing FS dewaterability (as capillary suction time). In this context, we evaluated FS degradation during anaerobic storage, the effect of anaerobic storage time on EPS, EPS fractions and particle size distribution, and the effect of variations in these factors on FS dewaterability. Variations in EPS, EPS fraction and particle size distribution during anaerobic storage were less than expected and average VS reduction of 20% was recorded over 7 weeks. Although anaerobic digestion was verified (biogas production), the results indicate that kinetics of degradation of FS is different from wastewater sludges. Comparatively, EPS fractions in FS were 70 - 75% lower and with higher fractions of humic-like substances than wastewater sludges. Although EPS significantly affects FS dewaterability, anaerobic storage time is not a predictor of dewaterability., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the coronavirus disease 2019 (COVID-19) has afflicted hundreds of millions of people in a worldwide pandemic. Several safe and effective COVID-19 vaccines are now available. However, the rapid emergence of variants and risk of viral escape from vaccine-induced immunity emphasize the need to develop broadly protective vaccines. A recombinant plant-derived virus-like particle vaccine for the ancestral COVID-19 (CoVLP) recently authorized by Canadian Health Authorities and a modified CoVLP.B1351 targeting the B.1.351 variant (both formulated with the adjuvant AS03) were assessed in homologous and heterologous prime-boost regimen in mice. Both strategies induced strong and broadly cross-reactive neutralizing antibody (NAb) responses against several Variants of Concern (VOCs), including B.1.351/Beta, B.1.1.7/Alpha, P.1/Gamma, B.1.617.2/Delta and B.1.1.529/Omicron strains. The neutralizing antibody (NAb) response was robust with both primary vaccination strategies and tended to be higher for almost all VOCs following the heterologous prime-boost regimen., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CD, SPR, GA, MAD, BJW and ST are either employees of Medicago Inc or receive salary support from Medicago Inc. CG is an employee of the GSK group of companies and reports ownership of GSK shares., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Inactivated influenza vaccines have struggled to provide consistent protection in older individuals. Circumventing immune senescence, an aging of the immune response characterized by weak humoral responses to vaccines, and unchecked inflammation during infection require novel immunization strategies. Plant-based virus-like particles (VLPs) bearing recombinant hemagglutinin proteins have been shown to provide protection in older animals in preclinical challenge studies, despite eliciting relatively low or absent humoral responses. The nature of the cellular response induced by these vaccines and its evolution during infection have not yet been fully characterized, however. Using a murine model that recapitulates features of human immune senescence, we assessed T cell responses to vaccination with a VLP bearing the hemagglutinin of H1N1/California 07/2009 (H1-VLP) before and after challenge in young and aged BALB/c mice (2 and 18 mo old, respectively). We report that two i.m. doses of H1-VLP (3 μg) vaccine 21 d apart generated H1-specific Th1 and Th2 cells associated with the prevention of prolonged pulmonary inflammation and mortality in both adult and aged mice. While investigating the regulation of cellular immunity, we identified a unique IL-1R1 + tissue-adapted regulatory T cell population in the lungs of both H1-VLP-vaccinated adult and aged mice, suggesting a novel regulatory T cell population associated with vaccine-mediated protection. Collectively, this study provides preclinical evidence that the plant-based H1-VLP vaccine may act, in part, by preventing exacerbated immune responses against influenza A., (Copyright © 2022 The Authors.)

Background: Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine., Methods: In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases., Results: A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%)., Conclusions: The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.)., (Copyright © 2022 Massachusetts Medical Society.)

Introduction: The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients., Methods: COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated., Results: As of 25 September 2021, 245 of 1703 patients (14.4%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19-affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious (n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover., Conclusion: COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon., (© 2022. The Author(s).)