Targeted Vaccination Strategies Research Articles

A targeted vaccination strategy based on dynamic community detection for epidemic networks

A targeted vaccination strategy based on dynamic community detection for epidemic networks

Accelerating COVID-19 Vaccination Among People Living With HIV and Health Care Workers in Tanzania: A Case Study.

There is limited evidence on COVID-19 vaccination uptake among people living with HIV (PLHIV) and health care workers (HCWs), with the current evidence concentrated in high-income countries. There is also limited documentation in the published literature regarding the feasibility and lessons from implementing targeted vaccination strategies to reach PLHIV and HCWs in low- and middle-income countries. We designed and implemented multifaceted strategies to scale up targeted COVID-19 vaccination among PLHIV and HCWs in 11 administrative regions on the mainland of Tanzania plus Zanzibar. An initial 6-week intensification strategy was implemented using a diverse partnership model comprising key stakeholders at the national- and subnational levels. A layered package of strategies included expanding the number of certified vaccinators, creating vaccination points within HIV clinics, engaging HCWs to address their concerns, and building the capacity of HCWs as "champions" to promote and facilitate vaccination. We then closely monitored COVID-19 vaccination uptake in 562 high-volume HIV clinics. Between September 2021 and September 2022, the proportion of fully vaccinated adult PLHIV increased from <1% to 97% and fully vaccinated HCWs increased from 23% to 80%. Our intra-action review highlighted the importance of leveraging a strong foundation of existing partnerships and platforms, integrating COVID-19 vaccination points within HIV clinics, and refining strategies to increase vaccination demand while ensuring continuity of vaccine supply to meet the increased demand. Lessons from Tanzania can inform targeted vaccination of vulnerable groups in future health emergencies.

Influenza Vaccination Coverage among People with Self-Reported Cardiovascular Diseases-Findings from the Hungarian Implementation of the European Health Interview Survey.

Worldwide, cardiovascular diseases are the leading cause of mortality. This has significant implications for public health. Influenza, a common infectious disease, poses an increased risk for individuals with chronic conditions, such as cardiovascular diseases. However, little is known about influenza vaccination coverage in this group. This study utilized data from the Hungarian implementation of the European Health Interview Survey to assess influenza vaccination coverage and its determinants among cardiovascular respondents from 2009 to 2019. The findings reveal a downward trend in the vaccination rates over the years (from 24% to 21%), despite the availability of free vaccination in Hungary for this high-risk population. The main factors influencing low influenza vaccine uptake were identified, as follows: young age, a lower level of education, good self-perceived health status, smoking, a lower frequency of medical visits, and not suffering from respiratory diseases. Addressing these disparities necessitates targeted vaccination strategies supported by enhanced education, better access to healthcare services, and the promotion of preventive healthcare measures. Improving vaccination coverage among patients with cardiovascular diseases is imperative for reducing influenza-related morbidity and mortality. This highlights the importance of comprehensive public health interventions and healthcare provider engagement in promoting vaccination among groups at increased risk.

Effectiveness of Sinopharm's BBIBP-CorV Booster Vaccination against COVID-19-Related Severe and Critical Cases and Deaths in Morocco during the Omicron Wave.

This study investigates the effectiveness of the 1st booster dose against COVID-19 severe and critical hospitalizations and deaths occurring due to the Omicron wave in Morocco. This study uses nationally representative data on COVID-19 from 15 December 2021 to 31 January 2022. The aim is to investigate the effectiveness of the inactivated COVID-19 vaccine BBIBP-CorV (Sinopharm) 1st booster dose against the Omicron wave in Morocco using real-world data established from nationally representative statistics on COVID-19 cases, deaths and vaccinations. The screening method was used to estimate vaccine effectiveness against COVID-19 severe or critical hospitalization and COVID-19-related deaths. The data were grouped by, age subgroup, sex, week, and geographical area and were analyzed using binary logistic regression with an offset for vaccine coverage. The overall BBIBP-CorV VE estimate is 89% (95% CI 85 to 92) effective in curbing COVID-19 deaths, and 81% (95% CI 78 to 84 in curbing COVID-19 severe/critical hospitalizations. Death-related VE estimate was 86% (95% CI 81 to 90) for patients aged ≥65 years, 96% (95% CI 90 to 98) for those aged <65 years, 95% (95% CI 88 to 98) in no-risk factor patients, 91% (95% CI 85 to 94) with 1 risk factor, 90% (95% CI 83 to 95) with 2 risk factors, and 72% (95% CI 52 to 84) in patients with 3 risk factors and more. Severe/critical hospitalization VE estimate was 78% (95% CI 74 to 82) for patients aged ≥65 years, 87% (95% CI 82 to 90) for those aged <65 years, 86% (95% CI 80 to 90) in no-risk factor patients, 80% (95% CI 73 to 84) with 1 risk factor, 80% (95% CI 70 to 85) with 2 risk factors, and 80% (95% CI 68 to 86) in patients with 3 risk factors and more. BBIBP-CorV boosters are effective in increasing protection against the Omicron variant-related COVID-19 deaths and severe/critical hospitalizations. The protection is reduced with older age and higher risk factors. These findings emphasize the importance of targeted vaccination strategies for different demographic groups and underscore the protective benefits of the first booster BBIBP-CorV vaccine.

Acceptability, cost-effectiveness, and capacity of a facility-based seasonal influenza vaccination among high-risk groups: a study protocol in selected tertiary care hospitals of Bangladesh

BackgroundIn Bangladesh, seasonal influenza imposes considerable disease and economic burden, especially for those at high-risk of severe disease. The most successful approach for influenza prevention is the administration of a vaccine. Many poor and middle-income nations, including Bangladesh, do not have a national strategy or program in place for seasonal influenza vaccines, despite the World Health Organization’s (WHO) advice to prioritize high-risk populations. Additionally, there is a scarcity of substantial data on the cost-effectiveness of seasonal influenza vaccination in these countries. The aim of our study is to determine acceptability, health beliefs, barriers, and intention of receiving influenza vaccine among high-risk populations, assess the cost-effectiveness of implementing a facility-based seasonal influenza vaccination programme, and investigate the required capacity for a potential seasonal influenza vaccination programme.MethodsWe will undertake this study following STROBE guidelines. We will conduct the study in inpatient and outpatient departments of three selected tertiary-level hospitals leveraging the ongoing hospital-based influenza surveillance (HBIS) platform. The study population will include the WHO-defined four high-risk groups excluding healthcare workers: children six months to eight years, pregnant women, elderly ≥ 60 years, and adults with chronic diseases. We will collect quantitative data on participants’ acceptability, health beliefs, barriers, and vaccination intentions using the health belief model (HBM) from patients meeting the criteria for high-risk populations attending two public tertiary-level hospitals. In one of the two public tertiary-level hospitals, we will arrange an influenza vaccination campaign before the influenza season, where the vaccine will be offered free of cost to high-risk patients, and in the second hospital, vaccination will not be offered. Both the vaccinated and unvaccinated participants will then be followed-up once a month for one year to record any influenza-like illness, hospitalization, and death. Additional data for objective two will be collected from patients with symptoms of influenza-like illness (ILI) and severe acute respiratory infection (SARI) at one public and one private hospital to determine both direct and indirect costs associated with influenza illness. We will estimate the required number of influenza vaccines, safe injections, and total storage volume utilizing secondary data. We will use a deterministic Markov decision-analytic model to estimate the cost-effectiveness of facility-based influenza vaccination in Bangladesh.DiscussionThe results of this study will enable the National Immunization Technical Advisory Group and the Ministry of Health & Family Welfare of Bangladesh to decide what steps to take to develop and implement an influenza vaccination strategy targeting high-risk populations.Trial registrationThe Clinicaltrials.gov registration number is NCT05996549. The registration for the protocol version 2.0 took place in August 2023, with the initial participant being enrolled in March 2022.

Having a real say: findings from first nations community panels on pandemic influenza vaccine distribution

BackgroundRecent deliberations by Australian public health researchers and practitioners produced an ethical framework of how decisions should be made to distribute pandemic influenza vaccine. The outcome of the deliberations was that the population should be considered in two categories, Level 1 and Level 2, with Level 1 groups being offered access to the pandemic influenza vaccine before other groups. However, the public health researchers and practitioners recognised the importance of making space for public opinion and sought to understand citizens values and preferences, especially First Nations peoples.MethodsWe conducted First Nations Community Panels in two Australian locations in 2019 to assess First Nations people’s informed views through a deliberative process on pandemic influenza vaccination distribution strategies. Panels were asked to make decisions on priority levels, coverage and vaccine doses.ResultsTwo panels were conducted with eighteen First Nations participants from a range of ages who were purposively recruited through local community networks. Panels heard presentations from public health experts, cross-examined expert presenters and deliberated on the issues. Both panels agreed that First Nations peoples be assigned Level 1 priority, be offered pandemic influenza vaccination before other groups, and be offered two doses of vaccine. Reasons for this decision included First Nations people’s lives, culture and families are important; are at-risk of severe health outcomes; and experience barriers and challenges to accessing safe, quality and culturally appropriate healthcare. We found that communication strategies, utilising and upskilling the First Nations health workforce, and targeted vaccination strategies are important elements in pandemic preparedness and response with First Nations peoples.ConclusionsFirst Nations Community Panels supported prioritising First Nations peoples for pandemic influenza vaccination distribution and offering greater protection by using a two-dose full course to fewer people if there are initial supply limitations, instead of one dose to more people, during the initial phase of the vaccine roll out. The methodology and findings can help inform efforts in planning for future pandemic vaccination strategies for First Nations peoples in Australia.

Mandatory Vaccination against COVID-19: Qualitative Analysis of Responses to Open-Ended Questions

The mandatory COVID-19 vaccination has been suggested as a strategy to increase vaccination uptake; however, there are doubts about its legitimacy as a measure. This study aimed to explore in depth the opinions of the Cypriot population regarding mandatory vaccination against COVID-19. Qualitative analysis of responses to an open-ended question was included as part of an anonymous, online, cross-sectional survey of the general population of Cyprus. A thematic analysis was performed by reading the responses and developing a coding frame. Descriptive analysis was performed on the sociodemographic and COVID-19-vaccine-related information. A total of 311 participants responded to the open-ended question, and the thematic analysis yielded two main themes: “Vaccination Perceptions and Challenges” and “Mandatory Vaccination Policies and Societal Impact.” Within these themes, participants expressed diverse opinions on universal and targeted mandatory vaccination, highlighting concerns about insufficient research, gaps in communication, and potential side effects. Views also varied on topics such as protective measures, interdisciplinary collaboration, vaccine side effects, human rights, and societal divisions. Criticisms encompassed political motives, skepticism towards the pandemic, and considerations of individual freedoms. In summary, the findings highlighted the intricate and varied perspectives surrounding the issue of mandatory COVID-19 vaccination, which can be valuable for policymakers and public health officials in designing targeted vaccination strategies. To optimize vaccination programs, policymakers and public health officials should prioritize trust, communication, and individual autonomy.

COVID’s First and Second Waves in India: Lessons and Policy Implications

In this article, we argue that in a supply-deficient situation, a vaccination strategy that makes use of an analysis of the different stages of the COVID waves and the pattern of their geographical spread can prove to be far more effective than the current non-transparent mechanism of inter-state allocation of the vaccines. We divide the spread of the COVID waves into three stages: (a) seeding stage, (b) explosion stage and (c) subsiding and diffusion stages. In the seeding stage, two critical determinants of seeding the virus into the population are (a) the inter-state pattern of arrival of international passengers and (b) the inter-state pattern of the continuing active COVID-affected population from the previous wave. The explosion stage induces a policy response in the form of lockdowns which is followed by the wave starting to subside. But the lockdown also results in the migration of labour out of the state into the rural and less populated areas, leading to the diffusion stage. We advocate a vaccination strategy targeting universal coverage with strategic sequencing in which prioritisation is given to ‘saturation vaccination’ of high-density and high COVID-intensity urban areas. This would not only minimise the economic costs in terms of duration and spread of lockdowns but also the pressures on the inadequate health infrastructure in terms of availability of hospital beds, ambulances, oxygen and drugs. This strategy may be implemented in curbing the COVID’s subsequent waves which may hit India while its population is still only partially vaccinated.

Differential T-cell and antibody responses induced by mRNA versus adenoviral vectored COVID-19 vaccines in patients with immunodeficiencies.

Immunodeficient patients (IDPs) are at higher risk of contracting severe coronavirus disease 2019 (COVID-19). Targeted vaccination strategies have been implemented to enhance vaccine-induced protection. In this population, however, clinical effectiveness is variable and the duration of protection unknown. We sought to better understand the cellular and humoral immune responses to mRNA and adenoviral vectored COVID-19 vaccines in patients with immunodeficiency. Immune responses to severe acute respiratory syndrome coronavirus 2 spike were assessed after 2 doses of homologous ChAdOx1-nCoV-19 or BNT162b2 vaccines in 112 infection-naive IDPs and 131 healthy health care workers as controls. Predictors of vaccine responsiveness were investigated. Immune responses to vaccination were low, and virus neutralization by antibody was not detected despite high titer binding responses in many IDPs. In those exhibiting response, the frequency of specific T-cell responses in IDPs was similar to controls, while antibody responses were lower. Sustained vaccine specific differences were identified: T-cell responses were greater in ChAdOx1-nCoV-19- compared to BNT162b2-immunized IDPs, and antibody binding and neutralization were greater in all cohorts immunized with BNT162b2. The positive correlation between T-cell and antibody responses was weak and increased with subsequent vaccination. Immunodeficient patients have impaired immune responses to mRNA and viral vector COVID-19 vaccines that appear to be influenced by vaccine formulation. Understanding the relative roles of T-cell- and antibody-mediated protection as well as the potential of heterologous prime and boost immunization protocols is needed to optimize the vaccination approach in these high-risk groups.

Patient characteristics and prediction of CoViD-19 in-hospital mortality: a retrospective cohort study in Crete, Greece before and after the onset of a targeted vaccination strategy in 2021

Background: CoviD-19 in-hospital mortality rates show variations across time, setting, patient populations and health-systems. Aim: The aim of the present study was to explore the association of patient characteristics with in-hospital mortality taking into consideration temporal changes of CoViD-19 prevention and treatment, focusing on the negative predictive value of specific biomarker thresholds for death and oxygen requirements. Methods: This retrospective study included a sample of 425 vaccine-naive patients hospitalized for CoViD-19 in Crete, Greece. Time-specific mortality rates and negative predictive values of biomarkers on admission were calculated. The association of patient characteristics with mortality was assessed using multivariate logistic regression models. Results: The overall in hospital case fatality rate (CFR) was 19.53%. The in-hospital CFR [95% CI] dropped from 22.74% [17.96-27.52] to 11.9% [6.17-17.63] before and after 31/03/2021, as did the mean age of hospitalized patients. LDH &amp; D-dimers ≥240 or ≥0.5), CRP &amp; D-dimers (≥3 or ≥0.5), CRP &amp; Ferritin (≥3 or ≥205) had negative predictive values [95% CI] for mortality of 100% [86.7-100], 96.1% [80.3-99.9] and 95.4% [84.5-99.4] %, but the respective negative predictive values for oxygen requirements were 19.2% [6.5-39.3], 19.2% [6.5-39.3] and 27.2% [14.9-42.7] . Conclusion: A decreasing trend of in-hospital case fatality rates over the course of our study was associated with a decreasing age of hospitalized patients, which could be associated with community vaccination uptake in people over 60 in Greece through reduction of persons “susceptible” to severe disease. Mortality prediction formulas incorporating biomarkers should be used cautiously for the risk stratification of patients with CoViD-19 in the setting of the emergency department assessment.

Herding behavior in COVID-19 vaccine hesitancy in rural Zimbabwe: The moderating role of health information under heterogeneous household risk perceptions

COVID-19 vaccine hesitancy poses a global health threat by potentially delaying the attainment of herd immunity to attenuate infection and transmission. Most governments across the world are engrossed with formulating strategies to surmount conservative group behavior such as vaccine hesitancy typical under risky and uncertain situations such as in the case of COVID-19. This paper examines herding behavior in vaccine hesitancy with a special focus on the moderating role of household access to health information from village health workers under different risk perceptions. We use the 2021 Zimbabwe Vulnerability Assessment Committee cross-section household national survey consisting of 13, 583 valid observations. Our major findings indicate that herding behavior plays a role in rural households’ hesitancy to COVID-19 vaccine inoculation. Furthermore, whilst access to health information from village health workers reduces herding behavior in vaccine hesitancy, it does so more when the household perceives itself to be at high risk of contracting COVID-19. Analysing herding behavior in vaccine hesitancy can help policymakers develop more targeted vaccination strategies, such as promoting access to health information through channels like village health workers, especially for households at high risk of contracting COVID-19.

Effect of Glycan Shift on Antibodies against Hepatitis C Virus E2 412-425 Epitope Elicited by Chimeric sHBsAg-Based Virus-Like Particles.

Two of the most important mechanisms of hepatitis C virus (HCV) immune evasion are the high variability of the amino acid sequence and epitope shielding via heavy glycosylation of the envelope (E) proteins. Previously, we showed that chimeric sHBsAg (hepatitis B virus [HBV] small surface antigen)-based virus-like particles (VLPs) carrying highly conserved epitope I from the HCV E2 glycoprotein (sHBsAg_412-425) elicit broadly neutralizing antibodies (bnAbs). However, many reports have identified escape mutations for such bnAbs that shift the N-glycosylation site from N417 to N415. This shift effectively masks the recognition of epitope I by antibodies raised against the wild-type glycoprotein. To investigate if glycan-shift-mediated immune evasion could be overcome by targeted vaccination strategies, we designed sHBsAg-based VLPs carrying epitope I with an N417S change (sHBsAg_N417S). Studies in BALB/c mice revealed that both sHBsAg_412-425 and sHBsAg_N417S VLPs were immunogenic, eliciting antibodies that recognized peptides encompassing epitope I regardless of the N417S change. However, we observed substantial differences in E1E2 glycoprotein binding and cell culture-derived HCV (HCVcc) neutralization between the sera elicited by sHBsAg_412-425 and those elicited by sHBsAg_N417S VLPs. Our results suggest a complex interplay among antibodies targeting epitope I, the E1E2 glycosylation status, and the epitope or global E1E2 conformation. Additionally, we observed striking similarities in the E1E2 glycoprotein binding patterns and HCVcc neutralization between sHBsAg_412-425 sera and AP33, suggesting that the immunization of mice with sHBsAg_412-425 VLPs can elicit AP33-like antibodies. This study emphasizes the role of antibodies against epitope I and represents an initial effort toward designing an antigen that elicits an immune response against epitope I with a glycan shift change. IMPORTANCE Epitope I, located within amino acids 412 to 423 of the HCV E2 glycoprotein, is an important target for an epitope-based HCV vaccine. One interesting feature of epitope I is the N417 glycosylation site, where a single change to S417 or T417 can shift the glycosylation site to position N415. This shift can effectively prevent the binding of broadly neutralizing antibodies targeting epitope I. Aiming to overcome glycan-shift-mediated immune evasion, we constructed sHBsAg_N417S VLPs carrying E2 epitope I, with N417S, and compared them with VLPs carrying wild-type epitope I. We show that antibodies elicited by the sHBsAg-based VLPs presenting two variants of the 412-425 epitope targeted two distinct glycan variants of the HCV E1E2 heterodimer. Our study suggests that due to the conformational flexibility of the E2 glycoprotein and epitope I, future vaccine antigens should elicit antibodies targeting more than one conformation and glycosylation variant of the 412-423 epitope.

CXCR5+PD-1++ CD4+ T cells colonize infant intestines early in life and promote B cell maturation.

Gastrointestinal infections are a major cause for serious clinical complications in infants. The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++ CD4+ T cells (TFH cells). We investigated the ontogeny of CXCR5+PD-1++ CD4+ T cells in human intestines. While CXCR5+PD-1++ CD4+ T cells were absent in fetal intestines, CXCR5+PD-1++ CD4+ T cells increased after birth and were abundant in infant intestines, resulting in significant higher numbers compared to adults. These findings were supported by scRNAseq analyses, showing increased frequencies of CD4+ T cells with a TFH gene signature in infantintestines compared to blood. Co-cultures of autologous infant intestinal CXCR5+PD-1+/-CD4+ T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B cells. Taken together, we demonstrate that functional TFH cells are numerous in infant intestines, making them a promising target for oral pediatric vaccine strategies.

HIV-1 CD4-binding site germline antibody–Env structures inform vaccine design

BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4-binding site (CD4bs) bNAbs. To understand how SHMs correlate with BG24 neutralization of HIV-1, we report 4.1 Å and 3.4 Å single-particle cryo-EM structures of two inferred germline (iGL) BG24 precursors complexed with engineered Env-based immunogens lacking CD4bs N-glycans. Structures reveal critical Env contacts by BG24iGL and identify antibody light chain structural features that impede Env recognition. In addition, biochemical data and cryo-EM structures of BG24iGL variants bound to Envs with CD4bs glycans present provide insights into N-glycan accommodation, including structural modes of light chain adaptations in the presence of the N276gp120 glycan. Together, these findings reveal Env regions critical for germline antibody recognition and potential sites to alter in immunogen design.

Risk factors associated with SARS-CoV-2 infection in a multiethnic cohort of United Kingdom healthcare workers (UK-REACH): A cross-sectional analysis.

Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs. We conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021. We used logistic regression to examine associations of demographic, household, and occupational risk factors with SARS-CoV-2 infection (defined by polymerase chain reaction (PCR), serology, or suspected COVID-19) in a diverse group of HCWs. The primary exposure of interest was self-reported ethnicity. Among 10,772 HCWs who worked during the first UK national lockdown in March 2020, the median age was 45 (interquartile range [IQR] 35 to 54), 75.1% were female and 29.6% were from ethnic minority groups. A total of 2,496 (23.2%) reported previous SARS-CoV-2 infection. The fully adjusted model contained the following dependent variables: demographic factors (age, sex, ethnicity, migration status, deprivation, religiosity), household factors (living with key workers, shared spaces in accommodation, number of people in household), health factors (presence/absence of diabetes or immunosuppression, smoking history, shielding status, SARS-CoV-2 vaccination status), the extent of social mixing outside of the household, and occupational factors (job role, the area in which a participant worked, use of public transport to work, exposure to confirmed suspected COVID-19 patients, personal protective equipment [PPE] access, aerosol generating procedure exposure, night shift pattern, and the UK region of workplace). After adjustment, demographic and household factors associated with increased odds of infection included younger age, living with other key workers, and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.59, 95% CI 2.11 to 3.18 for ≥21 patients per week versus none), working in a nursing or midwifery role (1.30, 1.11 to 1.53, compared to doctors), reporting a lack of access to PPE (1.29, 1.17 to 1.43), and working in an ambulance (2.00, 1.56 to 2.58) or hospital inpatient setting (1.55, 1.38 to 1.75). Those who worked in intensive care units were less likely to have been infected (0.76, 0.64 to 0.92) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known risk factors. This study is limited by self-selection bias and the cross sectional nature of the study means we cannot infer the direction of causality. We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection among UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic. The study was prospectively registered at ISRCTN (reference number: ISRCTN11811602).

Identification of microRNAs in the Lyme Disease Vector Ixodes scapularis.

MicroRNAs (miRNAs) are a class of small non-coding RNAs involved in many biological processes, including the immune pathways that control bacterial, parasitic, and viral infections. Pathogens probably modify host miRNAs to facilitate successful infection, so they might be useful targets for vaccination strategies. There are few data on differentially expressed miRNAs in the black-legged tick Ixodes scapularis after infection with Borrelia burgdorferi, the causative agent of Lyme disease in the United States. Small RNA sequencing and qRT-PCR analysis were used to identify and validate differentially expressed I. scapularis salivary miRNAs. Small RNA-seq yielded 133,465,828 (≥18 nucleotides) and 163,852,135 (≥18 nucleotides) small RNA reads from Borrelia-infected and uninfected salivary glands for downstream analysis using the miRDeep2 algorithm. As such, 254 miRNAs were identified across all datasets, 25 of which were high confidence and 51 low confidence known miRNAs. Further, 23 miRNAs were differentially expressed in uninfected and infected salivary glands: 11 were upregulated and 12 were downregulated upon pathogen infection. Gene ontology and network analysis of target genes of differentially expressed miRNAs predicted roles in metabolic, cellular, development, cellular component biogenesis, and biological regulation processes. Several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including sphingolipid metabolism; valine, leucine and isoleucine degradation; lipid transport and metabolism; exosome biogenesis and secretion; and phosphate-containing compound metabolic processes, were predicted as targets of differentially expressed miRNAs. A qRT-PCR assay was utilized to validate the differential expression of miRNAs. This study provides new insights into the miRNAs expressed in I. scapularis salivary glands and paves the way for their functional manipulation to prevent or treat B. burgdorferi infection.

CD4+ T-cell epitope-based heterologous prime-boost vaccination potentiates anti-tumor immunity and PD-1/PD-L1 immunotherapy

BackgroundAntitumor therapeutic vaccines are generally based on antigenic epitopes presented by major histocompatibility complex (MHC-I) molecules to induce tumor-specific CD8+ T cells. Paradoxically, continuous T cell receptor (TCR) stimulation from...

Social Vulnerability and Rurality Associated With Higher Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection–Induced Seroprevalence: A Nationwide Blood Donor Study—United States, July 2020–June 2021

BackgroundMost studies on health disparities during COVID-19 pandemic focused on reported cases and deaths, which are influenced by testing availability and access to care. This study aimed to examine SARS-CoV-2 antibody seroprevalence in the U.S. and its associations with race/ethnicity, rurality, and social vulnerability over time.MethodsThis repeated cross-sectional study used data from blood donations in 50 states and Washington, D.C. from July 2020 through June 2021. Donor ZIP codes were matched to counties and linked with Social Vulnerability Index (SVI) and urban-rural classification. SARS-CoV-2 antibody seroprevalences induced by infection and infection-vaccination combined were estimated. Association of infection-induced seropositivity with demographics, rurality, SVI, and its four themes were quantified using multivariate regression models.FindingsWeighted seroprevalence differed significantly by race/ethnicity and rurality, and increased with increasing social vulnerability. During the study period, infection-induced seroprevalence increased from 1.6% to 27.2% and 3.7% to 20.0% in rural and urban counties, respectively, while rural counties had lower combined infection- and vaccination-induced seroprevalence (80.0% vs. 88.1%) in June 2021. Infection-induced seropositivity was associated with being Hispanic, non-Hispanic Black, and living in rural or higher socially vulnerable counties, after adjusting for demographic and geographic covariates.ConclusionThe findings demonstrated increasing SARS-CoV-2 seroprevalence in the U.S. across all geographic, demographic, and social sectors. The study illustrated disparities by race-ethnicity, rurality, and social vulnerability. The findings identified areas for targeted vaccination strategies and can inform efforts to reduce inequities and prepare for future outbreaks.

A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination.

Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem-specific epitopes have been extensively characterized for HA subtypes H1 and H5 in humans. H2N2 influenza virus circulated 50 years ago and represents a pandemic threat due to the lack of widespread immunity, but, unlike H1 and H5, the H2 HA stem contains Phe45HA2 predicted to sterically clash with HA stem-binding antibodies characterized to date. To understand the effect of Phe45HA2, we compared the HA stem-specific B cell response in post hoc analyses of two phase 1 clinical trials, one testing vaccination with an H2 ferritin nanoparticle immunogen ( NCT03186781 ) and one with an inactivated H5N1 vaccine ( NCT01086657 ). In H2-naive individuals, the magnitude of the B cell response was equivalent, but H2-elicited HA stem-binding B cells displayed greater cross-reactivity than those elicited by H5. However, in individuals with childhood H2 exposure, H5-elicited HA stem-binding B cells also displayed high cross-reactivity, suggesting recall of memory B cells formed 50 years ago. Overall, we propose that a one-residue difference on an HA immunogen can alter establishment and expansion of broadly neutralizing memory B cells. These data have implications for stem-based universal influenza vaccination strategies.

Antibodies directed towards neuraminidase restrict influenza virus replication in primary human bronchial epithelial cells.

Influenza neuraminidase (NA) is implicated in various aspects of the virus replication cycle and therefore is an attractive target for vaccination and antiviral strategies. Here we investigated the potential for NA-specific antibodies to interfere with A(H1N1)pdm09 replication in primary human airway epithelial (HAE) cells. Mouse polyclonal anti-NA sera and a monoclonal antibody could block initial viral entry into HAE cells as well as egress from the cell surface. NA-specific polyclonal serum also reduced virus replication across multiple rounds of infection. Restriction of virus entry correlated with the ability of the serum or monoclonal antibody to mediate neuraminidase inhibition (NI). Finally, human sera with NI activity against the N1 of A(H1N1)pdm09 could decrease H6N1 virus infection of HAE cells, highlighting the potential contribution of anti-NA antibodies in the control of influenza virus infection in humans.