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.

Age and Ageing During the COVID-19 Pandemic; Challenges to Public Health and to the Health of the Public

The distribution of the SARS-CoV-2 virus has reached pandemic proportions. While COVID-19 can affect anyone, it is particularly hazardous for those with “co-morbidities.” Older age is an especially strong and independent risk factor for hospital and ICU admission, mechanical ventilation and death. Health systems must protect persons at any age while paying particular attention to those with risk factors. However, essential freedoms must be respected and social/psychological needs met for those shielded. The example of the older population in Israel may provide interesting public health lessons. Relatively speaking, Israel is a demographically young country, with only 11.5% of its population 65 years and older as compared with the OECD average of >17%. As well, a lower proportion of older persons is in long-term institutions in Israel than in most other OECD countries. The initiation of a national program to protect older residents of nursing homes and more latterly, a successful vaccine program has resulted in relatively low rates of serious COVID-19 related disease and mortality in Israel. However, the global situation remains unstable and the older population remains at risk. The rollout of efficacious vaccines is in progress but it will probably take years to cover the world's population, especially those living in low- and middle-income countries. Every effort must be made not to leave these poorer countries behind. Marrying the principles of public health (care of the population) with those of geriatric medicine (care of the older individual) offers the best way forward.

A Pervasive Review on New Advancements of Nano Vaccines on Covid-19 Pandemic

The infection that causes COVID-19 may be a pathogen referred to as severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) and is believed to possess originated from China's Wuhan Province. The rapid spread of coronavirus disease 2019 (COVID-19) has become a worldwide concern, with the planet Health Organization (WHO) declaring it an epidemic on March, 2020. To enter the cells, SARS-CoV-2 S requires angiotensin-converting enzyme 2 (ACE2). Many existing vaccines have drawbacks like insufficient system stimulation, in vivo instability, high toxicity, the need for a chilly chain, and multiple administration. A nanotechnology is an efficient tool for addressing these issues. A successful vaccine against SARS-CoV-2 infection is predicted to stimulate innate and adaptive immune responses and protects against severe sorts of coronavirus disease 2019 (COVID-19). Different strategies are introduced because the go after an efficient and safe vaccination has begun. Currently, the foremost common vaccine types studied in clinical trials include viral vector-based vaccinations, genetic vaccines, attenuated vaccines, and protein-based vaccines. during this review, we cover the foremost promising anti-COVID-19 vaccine clinical trials also as various vaccination strategies to shed more light on the continued clinical trials. it's also discussed how nanotechnology is often wont to better understand the pathology of the present pandemic, also as how our understanding of SARS-CoV-2 cellular uptake and toxicity can influence future nanotoxicological considerations and nanomedicine design of safe yet effective nanomaterials.

Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies

Both vaccine “take” and neutralizing antibody (nAb) titer are historical correlates for vaccine-induced protection from smallpox. We analyzed a subset of samples from a phase 2a trial of three DNA/HIV-1 primes and a recombinant Tiantan vaccinia virus-vectored (rTV)/HIV-1 booster and found that a proportion of participants showed no anti-vaccinia nAb response to the rTV/HIV-1 booster, despite successful vaccine “take.” Using a rich transcriptomic and vaccinia-specific immunological dataset with fine kinetic sampling, we investigated the molecular mechanisms underlying nAb response. Blood transcription module analysis revealed the downregulation of the activator protein 1 (AP-1) pathway in responders, but not in non-responders, and the upregulation of T-cell activation in responders. Furthermore, transcriptional factor network reconstruction revealed the upregulation of AP-1 core genes at hour 4 and day 1 post-rTV/HIV-1 vaccination, followed by a downregulation from day 3 until day 28 in responders. In contrast, AP-1 core and pro-inflammatory genes were upregulated on day 7 in non-responders. We speculate that persistent pro-inflammatory signaling early post-rTV/HIV-1 vaccination inhibits the nAb response.

Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide and led to approximately 4 million deaths as of August 2021. Despite successful vaccine development, treatment options are limited. A promising strategy to specifically target viral infections is to suppress viral replication through RNA interference (RNAi). Hence, we designed eight small interfering RNAs (siRNAs) targeting the highly conserved 5’-untranslated region (5’-UTR) of SARS-CoV-2. The most promising candidate identified in initial reporter assays, termed siCoV6, targets the leader sequence of the virus, which is present in the genomic as well as in all subgenomic RNAs. In assays with infectious SARS-CoV-2, it reduced replication by two orders of magnitude and prevented the development of a cytopathic effect. Moreover, it retained its activity against the SARS-CoV-2 alpha variant and has perfect homology against all sequences of the delta variant that were analyzed by bioinformatic means. Interestingly, the siRNA was even highly active in virus replication assays with the SARS-CoV-1 family member. This work thus identified a very potent siRNA with a broad activity against various SARS-CoV viruses that represents a promising candidate for the development of new treatment options.

Challenges and Prospects of Plant-Derived Oral Vaccines against Hepatitis B and C Viruses

Hepatitis B and C viruses chronically affect approximately 3.5% of the global population, causing more than 800,000 deaths yearly due to severe liver pathogenesis. Current HBV vaccines have significantly contributed to the reduction of chronic HBV infections, supporting the notion that virus eradication is a feasible public health objective in the near future. In contrast to HBV, a prophylactic vaccine against HCV infection is not available yet; however, intense research efforts within the last decade have significantly advanced the field and several vaccine candidates are shortlisted for clinical trials. A successful vaccine against an infectious disease of global importance must not only be efficient and safe, but also easy to produce, distribute, administer, and economically affordable to ensure appropriate coverage. Some of these requirements could be fulfilled by oral vaccines that could complement traditional immunization strategies. In this review, we discuss the potential of edible plant-based oral vaccines in assisting the worldwide fight against hepatitis B and C infections. We highlight the latest research efforts to reveal the potential of oral vaccines, discuss novel antigen designs and delivery strategies, as well as the limitations and controversies of oral administration that remain to be addressed to make this approach successful.

Effect of Two Unique Nanoparticle Formulations on the Efficacy of a Broadly Protective Vaccine Against Pseudomonas Aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of infections in humans. In addition to its innate antibiotic resistance, P. aeruginosa is very effective in acquiring resistance resulting in the emergence of multi-drug resistance strains and a licensed vaccine is not yet available. We have previously demonstrated the protective efficacy of a novel antigen PaF (Pa Fusion), a fusion of the type III secretion system (T3SS) needle tip protein, PcrV, and the first of two translocator proteins, PopB. PaF was modified to provide a self-adjuvanting activity by fusing the A1 subunit of the heat-labile enterotoxin from Enterotoxigenic E. coli to its N-terminus to give L-PaF. In addition to providing protection against 04 and 06 serotypes of P. aeruginosa, L-PaF elicited opsonophagocytic killing and stimulated IL-17A secretion, which have been predicted to be required for a successful vaccine. While monomeric recombinant subunit vaccines can be protective in mice, this protection often does not transfer to humans where multimeric formulations perform better. Here, we use two unique formulations, an oil-in-water (o/w) emulsion and a chitosan particle, as well as the addition of a unique TLR4 agonist, BECC438 (a detoxified lipid A analogue designated Bacterial Enzymatic Combinatorial Chemistry 438), as an initial step in optimizing L-PaF for use in humans. The o/w emulsion together with BECC438 provided the best protective efficacy, which correlated with high levels of opsonophagocytic killing and IL-17A secretion, thereby reducing the lung burden among all the vaccinated groups tested.

Understanding the Dynamics of SARS-CoV-2 Variants of Concern in Ontario, Canada: A Case Study

A year after the initial wild-type Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) strains began their devastation of the world, they were supplanted by new variants of concern (VOC). In Ontario, Canada, the wild type was overtaken first by the Alpha/B1.1.17 variant, and then by the Delta/B.1.617 variant. The principal objective of the present study is to develop and apply a much expanded Susceptible-Infection-Recovered-type model to better understand the spread of multiple VOC, and assess the effectiveness of vaccination and non-pharmaceutical interventions (NPI). The model represents competition among VOC, and reveals their mutual inhibitory effects. By separately tracking asymptomatic and symptomatic infections, model simulations identify a significant role of vaccine breakthrough in the spread of Delta. Furthermore, the severity of a Delta outbreak depends not only on the NPI and vaccination rate but also on the vaccine types. Alarmingly, despite Ontario’s existing NPI and relatively successful vaccine rollout, a future, more dangerous VOC could potentially infect a significant fraction of the province’s population and overwhelm the health care system. To stop that VOC, the province may need the simultaneous and rapid deployment of a third booster vaccine and stringent NPI.

Knowledge and Readiness of Community Health Volunteers to Lead Sensitization of Communities on COVID-19 Vaccination in Kenya: A Crosssectional Study

BackgroundVaccination is anticipated to bring the COVID-19 pandemic to an ultimate end. Community health volunteers (CHVs) are the link between communities and the formal health system and are therefore a vital factor in successful vaccine rollout in Kenya. However, the ability of CHVs to lead community sensitization on COVID-19 vaccination was uncertain. The aim of this study was to assess the knowledge of CHVs on COVID-19 vaccination, and determine if their knowledge is adequate to lead sensitization of communities in the national COVID-19 vaccination programme.MethodsThis was a mixed methods study comprising a cross-sectional survey and key informant interviews. Quantitative data were collected from 413 CHVs in four counties of Kenya through telephone interviews; 12 key informants were also interviewed through telephone interviews. SPSS version 25.0 and R script programming were utilised to analyse quantitative data. Qualitative data were analyzed using MAXQDA software.ResultsOf 413 CHVs surveyed, 82.3% felt inadequately informed to engage with communities on COVID-19 vaccination. There was a significant difference in the level of knowledge between CHVs in urban compared to rural counties (P=0.0005). The level of knowledge was also higher among more educated CHVs compared to less educated CHVs (OR=3.04, 95% CI: 2.47-3.61; p < 0.001). Knowledge on COVID-19 vaccine was higher in CHVs who had previously received accredited training on COVID-19 (OR=1.86, 95% CI: 1.28-2.45; p < 0.001) and this had a significant influence on CHV’s willingness to be vaccinated. CHVs with higher levels of knowledge were more likely to express readiness to engage with communities on COVID-19 vaccination than those with lesser knowledge (P=0.0001). ConclusionCHVs in four counties of Kenya did not have adequate knowledge on COVID-19 vaccination which is a major constraint to their work of mobilising communities to accept COVID-19 vaccination.

REACT-1 round 12 report: resurgence of SARS-CoV-2 infections in England associated with increased frequency of the Delta variant

Background England entered a third national lockdown from 6 January 2021 due to the COVID-19 pandemic. Despite a successful vaccine rollout during the first half of 2021, cases and hospitalisations have started to increase since the end of May as the SARS-CoV-2 Delta (B.1.617.2) variant increases in frequency. The final step of relaxation of COVID-19 restrictions in England has been delayed from 21 June to 19 July 2021. Methods The REal-time Assessment of Community Transmision-1 (REACT-1) study measures the prevalence of swab-positivity among random samples of the population of England. Round 12 of REACT-1 obtained self-administered swab collections from participants from 20 May 2021 to 7 June 2021; results are compared with those for round 11, in which swabs were collected from 15 April to 3 May 2021. Results Between rounds 11 and 12, national prevalence increased from 0.10% (0.08%, 0.13%) to 0.15% (0.12%, 0.18%). During round 12, we detected exponential growth with a doubling time of 11 (7.1, 23) days and an R number of 1.44 (1.20, 1.73). The highest prevalence was found in the North West at 0.26% (0.16%, 0.41%) compared to 0.05% (0.02%, 0.12%) in the South West. In the North West, the locations of positive samples suggested a cluster in Greater Manchester and the east Lancashire area. Prevalence in those aged 5-49 was 2.5 times higher at 0.20% (0.16%, 0.26%) compared with those aged 50 years and above at 0.08% (0.06%, 0.11%). At the beginning of February 2021, the link between infection rates and hospitalisations and deaths started to weaken, although in late April 2021, infection rates and hospital admissions started to reconverge. When split by age, the weakened link between infection rates and hospitalisations at ages 65 years and above was maintained, while the trends converged below the age of 65 years. The majority of the infections in the younger group occurred in the unvaccinated population or those without a stated vaccine history. We observed the rapid replacement of the Alpha (B.1.1.7) variant of SARS-CoV-2 with the Delta variant during the period covered by rounds 11 and 12 of the study. Discussion The extent to which exponential growth continues, or slows down as a consequence of the continued rapid roll-out of the vaccination programme, including to young adults, requires close monitoring. Data on community prevalence are vital to track the course of the epidemic and inform ongoing decisions about the timing of further lifting of restrictions in England.