Generation of High Quality Memory B Cells

Protection against pathogen re-infection is mediated, in large part, by two humoral cellular compartments, namely, long-lived plasma cells and memory B cells. Recent data have reinforced the importance of memory B cells, particularly in response to re-infection of different viral subtypes or in response with viral escape mutants. In regard to memory B cell generation, considerable advancements have been made in recent years in elucidating its basic mechanism, which seems to well explain why the memory B cells pool can deal with variant viruses. Despite such progress, efforts to develop vaccines that induce broadly protective memory B cells to fight against rapidly mutating pathogens such as influenza virus and HIV have not yet been successful. Here, we discuss recent advances regarding the key signals and factors regulating germinal center-derived memory B cell development and activation and highlight the challenges for successful vaccine development.

Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza

Recent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace of development and deployment of vaccine doses. Already demonstrated successfully for single antigen vaccines such as for COVID-19, this technology could be optimized for complex multi-antigen vaccines. Herein, utilizing multiple influenza antigens, we demonstrated the suitability of the mRNA therapeutic (MRT) platform for such applications. Seasonal influenza vaccines have three or four hemagglutinin (HA) antigens of different viral subtypes. In addition, influenza neuraminidase (NA), a tetrameric membrane protein, is identified as an antigen that has been linked to protective immunity against severe viral disease. We detail the efforts in optimizing formulations of influenza candidates that use unmodified mRNA encoding full-length HA or full-length NA encapsulated in lipid nanoparticles (LNPs). HA and NA mRNA-LNP formulations, either as monovalent or as multivalent vaccines, induced strong functional antibody and cellular responses in non-human primates and such antigen-specific antibody responses were associated with protective efficacy against viral challenge in mice.

Top Three Strategies of ss(+)RNA Plant Viruses: Great Opportunists and Ecosystem Tuners with a Small Genome

ss(+)RNA viruses represent the dominant group of plant viruses. They owe their evolutionary superiority to the large number of mutations that occur during replication, courtesy of RNA-dependent RNA polymerase. Natural selection rewards successful viral subtypes, whose effective tuning of the ecosystem regulates the interactions between its participants. Thus, ss(+)RNA viruses act as shuttles for the functionally important genes of the participants in symbiotic relationships within the ecosystem, of which the most common ecological triad is “plant–virus–insect”. Due to their short life cycle and large number of offspring, RNA viruses act as skillful tuners of the ecosystem, which benefits both viruses and the system as a whole. A fundamental understanding of this aspect of the role played by viruses in the ecosystem makes it possible to apply this knowledge to the creation of DNA insecticides. In fact, since the genes that viruses are involved in transferring are functionally important for both insects and plants, silencing these genes (for example, in insects) can be used to regulate the pest population. RNA viruses are increasingly treated not as micropathogens but as necessary regulators of ecosystem balance.

Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China

IntroductionPretreatment drug resistance (PDR) is becoming an obstacle to the success of ART. This study investigated the prevalence of PDR and the transmission clusters (TCs) of drug resistance mutations (DRMs) in two cities where drug abuse used to be high to describe the local HIV-1 transmission dynamics.MethodsPlasma samples were obtained from 1,027 ART-naïve patients in Guangxi. Viral subtypes and DRMs were identified. Transmission network and related factors were also determined.ResultsA total of 1,025 eligible sequences were obtained from Qinzhou (65.8%) and Baise (34.2%) cities. The predominant HIV-1 genotype was CRF08_BC (45.0%), followed by CRF01_AE (40.9%). The overall prevalence of PDR was 8.3%, and resistance to NNRTI was the most common. Putative links with at least one other sequence were found in 543/1,025 (53.0%) sequences, forming 111 clusters (2–143 individuals). The most prevalent shared DRMs included V106I (45.35%), V179D (15.1%), and V179E (15.1%). Clusters related to shared DRMs were more frequent and larger in CRF08_BC. The prevalence of shared DRMs increased with time, while the proportion of PDR gradually decreased. Age > 50 years was associated with clustering. Subtype CRF08_BC was more likely to have DRMs, PDR propagation, and DRM sharing.ConclusionPDR prevalence is moderate in this region. The association between PDR and subtype CRF08_BC suggested that DRMs spreading from injection drug users (IDUs) to heterosexuals (HETs) might be the major source of PDR in this region. Our findings highlight the significance of continuous surveillance of PDR.

Economic impacts of Bovine alphaherpesvirus 1 infection in Brazil: Meta-analysis based on epidemiological indicators

This study aimed to conduct a systematic review to estimate the economic impact of Bovine alphaherpesvirus 1 (BoAHV1) infection in Brazil using epidemiological indicators through a meta-analysis. Specific descriptors were used to retrieve studies from the Scopus, PubMed, Biblioteca Digital Brasileira de Teses e Dissertações, and Catálogo de Teses e Dissertações da Capes databases, selecting those that met the inclusion criteria established between the years 2000 and 2020. The selected studies were subjected to descriptive statistical analysis using prevalence data as the primary outcome with a 95% confidence interval (CI) with a meta-analysis of random effects and measures of heterogeneity, significance, magnitude of the effect, and measurement of publication bias. Abortion costs and estimates were calculated based on the prevalence of BoAHV1 infection in Brazil and the characteristics of the agent as viral subtypes that cause abortion, period of occurrence, average pregnancy rate, and morbidity applied to susceptible animals and animal replacement values. The results were obtained from 49 studies included for meta-analysis where a prevalence of BoAHV1 infection of 54.12% (95% CI: 49.07% - 59.26%) in the bovine population and 88.53% (95% CI: 82.97%–92.43%) was present. From the structured formula, it is estimated that 258,779 bovine abortions occur, which causes a total loss, based only on the occurrence of abortion, of US $ 48,402,244.00 to the country. It is noteworthy that because of the losses caused, strict control and eradication measures need to be implemented based on the elaboration of normative instruction that includes health education measures, vaccination, tests for traffic, and animal trade so that BoAHV1 infections do not continue to negatively impact national producers economically, productively, and socially.

HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: A systematic review and meta-analysis protocol

Background Some mutations in the HIV-1 Gag gene are known to confer resistance to ritonavir-boosted protease inhibitors (PI/r), but their clinical implications remain controversial. This review aims at summarizing current knowledge on HIV-1 Gag gene mutations that are selected under PI/r pressure and their distribution according to viral subtypes. Materials and methods Randomized and non-randomized trials, cohort and cross-sectional studies evaluating HIV-1 Gag gene mutations and protease resistance associated mutations, will all be included. Searches will be conducted (from January 2000 onwards) in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILAC), Web of Science, African Journals Online, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Hand searching of the reference lists of relevant reviews and trials will be conducted and we will also look for conference abstracts. Genotypic profiles of both Gag gene and the protease region as well as viral subtypes (especially B vs. non B) will all serve as comparators. Primary outcomes will be the “prevalence of Gag mutations” and the “prevalence of PI/r resistance associated mutations”. Secondary outcomes will be the “rate of treatment failure” and the distribution of Gag mutations according to subtypes. Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility, and extract data. If data permits, random effects models will be used where appropriate. This study will be reported according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta Analyses. Discussion This systematic review will help identify HIV-1 Gag gene mutations associated to PI/r-based regimen according to viral subtypes. Findings of this review will help to better understand the implications of the Gag gene mutations in PI/r treatment failure. This may later justify considerations of Gag-genotyping within HIV drug resistance interpretation algorithms in the clinical management of patients receiving PI/r regimens. Systematic review registration PROSPERO: CRD42019114851.

Phylogenetic Analysis of HIV-1 Shows Frequent Cross-Country Transmission and Local Population Expansions

Understanding of pandemics depends on characterization of pathogen collections from well-defined and demographically diverse cohorts. Since its emergence in Congo almost a century ago, HIV-1 has geographically spread and genetically diversified into distinct viral subtypes. Phylogenetic analysis can be used to reconstruct the ancestry of the virus to inform on the origin and distribution of subtypes. We sequenced two 3.6 kb amplicons of HIV-1 genomes from 3,197 participants in a clinical trial with consistent and uniform sampling at sites across 35 countries and analyzed our data with another 2,632 genomes that comprehensively reflects the HIV-1 genetic diversity. We used maximum likelihood phylogenetic analysis coupled with geographical information to infer the state of ancestors. The majority of our sequenced genomes (n=2,501) were either pure subtypes (A-D, F, G) or CRF01_AE. The diversity and distribution of subtypes across geographical regions differed; United States showed the most homogenous subtype population, whereas African samples were most diverse. We delineated transmission of the four most prevalent subtypes in our dataset (A, B, C, and CRF01_AE), and our results suggest both continuous and frequent transmission of HIV-1 over country borders, as well as single transmission events being the seed of endemic population expansions. Overall, we show that coupling of genetic and geographical information of HIV-1 can be used to understand origin and spread of pandemic pathogens.

Very little influenza in the WHO European Region during the 2020/21 season, weeks 40 2020 to 8 2021

Between weeks 40 2020 and 8 2021, the World Health Organization European Region experienced a 99.8% reduction in sentinel influenza virus positive detections (33/25,606 tested; 0.1%) relative to an average of 14,966/39,407 (38.0%; p < 0.001) over the same time in the previous six seasons. COVID-19 pandemic public health and physical distancing measures may have extinguished the 2020/21 European seasonal influenza epidemic with just a few sporadic detections of all viral subtypes. This might possibly continue during the remainder of the influenza season.

Identification and Prevalence of Phascolarctid Gammaherpesvirus Types 1 and 2 in South Australian Koala Populations

To determine Phascolarctid gammaherpesviruses (PhaHV) infection in South Australian koala populations, 80 oropharyngeal swabs from wild-caught and 87 oropharyngeal spleen samples and swabs from euthanased koalas were tested using two specific PCR assays developed to detect PhaHV-1 and PhaHV-2. In wild-caught koalas, active shedding of PhaHV was determined by positive oropharyngeal samples in 72.5% (58/80) of animals, of which 44.8% (26/58) had PhaHV-1, 20.7% (12/58) PhaHV-2 and 34.5% (20/58) both viral subtypes. In the euthanased koalas, systemic infection was determined by positive PCR in spleen samples and found in 72.4% (63/87) of koalas. Active shedding was determined by positive oropharyngeal results and found in 54.0% (47/87) of koalas. Koalas infected and actively shedding PhaHV-1 alone, PhaHV-2 alone or shedding both viral subtypes were 48.9% (23/47), 14.9% (7/47) and 36.2% (17/47), respectively. Only 45.9% (40/87) were not actively shedding, of which 40.0% (16/40) of these had systemic infections. Both wild-caught and euthanased koalas actively shedding PhaHV-2 were significantly more likely to be actively shedding both viral subtypes. Active shedding of PhaHV-2 had a significant negative correlation with BCS in the euthanased cohort, and active shedding of PhaHV-1 had a significant positive relationship with age in both wild-caught and euthanased cohorts.