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1.
AIDS Behav ; 2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2303990

ABSTRACT

We compared retention in care outcomes between a pre-COVID-19 (Apr19-Mar20) and an early-COVID-19 (Apr20-Mar21) period to determine whether the pandemic had a significant impact on these outcomes and assessed the role of patient sociodemographics in both periods in individuals enrolled in the Data for Care Alabama project (n = 6461). Using scheduled HIV primary care provider visits, we calculated a kept-visit measure and a missed-visit measure and compared them among the pre-COVID-19 and early-COVID-19 periods. We used logistic regression models to calculated odds ratios (OR) and accompanying 95% confidence intervals (CI). Overall, individuals had lowers odds of high visit constancy [OR (95% CI): 0.85 (0.79, 0.92)] and higher odds of no-shows [OR (95% CI): 1.27 (1.19, 1.35)] during the early-COVID-19 period. Compared to white patients, Black patients were more likely to miss an appointment and transgender people versus cisgender women had lower visit constancy in the early-COVID-19 period.

2.
AIDS Behav ; 2022 Sep 26.
Article in English | MEDLINE | ID: covidwho-2263111

ABSTRACT

The COVID-19 pandemic has disrupted sexual health services among those most vulnerable to HIV acquisition, such as adolescent men who have sex with men (AMSM). We sought to characterize the changes in sexual-risk behaviors, HIV and other STI testing, and pre-exposure prophylaxis (PrEP) use among a longitudinal cohort of AMSM aged 13 to 18 years before and during the COVID-19 pandemic. We observed a significant decline in HIV testing and a marginal decrease in other STI testing since the pandemic began in March 2020. Outreach efforts and innovative remote delivery of sexual health services are needed to support access to healthcare services among AMSM as the pandemic persists.


RESUMEN: La pandemia de COVID-19 ha afectado la prestación de servicios de salud sexual para los más vulnerables, tales como los hombres adolescentes que tienen relaciones sexuales con hombres (AMSM; por sus siglas en ingles). En una cohorte longitudinal de AMSM de 13 a 18 años, examinamos los cambios en comportamientos sexuales de alto riesgo, la prueba de VIH, las pruebas de otras enfermedades de transmisión sexual, y el uso de Profilaxis Preexposición (PrEP) para el VIH antes y durante la pandemia. Desde el inicio de la pandemia en marzo de 2020, observamos una disminución significativa en la frecuencia de pruebas de VIH y una disminución marginal en la frecuencia de pruebas de otras enfermedades de transmisión sexual. Mientras persista la pandemia, serán necesarios más esfuerzos de divulgación e innovaciones en la prestación remota de servicios de salud sexual para apoyar el acceso a dichos servicios por parte de AMSM.

3.
Microbes Infect ; : 105078, 2022 Nov 23.
Article in English | MEDLINE | ID: covidwho-2245025

ABSTRACT

The unprecedented success of mRNA vaccines in managing the COVID-19 pandemic raises the prospect of applying the mRNA platform to other viral diseases of humans and domesticated animals, which may lead to more efficacious vaccines for some agents. We briefly discuss reasons why mRNA vaccines achieved such success against COVID-19 and indicate what other virus infections and disease conditions might also be ripe for control using mRNA vaccines. We also evaluate situations where mRNA could prove valuable to rebalance the status of immune responsiveness and achieve success as a therapeutic vaccine approach against infections that induce immunoinflammatory lesions.

5.
AIDS Care ; : 1-7, 2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-2187163

ABSTRACT

ABSTRACTAlabama depends heavily on Ryan White HIV/AIDS Program (RWHAP) funding, yet patient enrollment at one large, RWHAP-funded, academically-affiliated HIV clinic in Alabama has steadily increased each year, with approximately 20% bypassing more proximal RWHAP clinics. To understand reasons why patients travel long distances and bypass closer clinics to receive care, we conducted eight focus groups over Zoom, each containing between 2-3 participants (n = 18) and applied thematic analysis to code the data. Primary themes included: (1) Reasons for Traveling Long Distances to Receive HIV Medical Care, (2) Experiences with HIV Medical Care during the COVID-19 Pandemic, and (3) Travel Challenges. Some participants were attracted by the clinic's one-stop-shop model, while others eschewed local clinics to avoid status disclosure. An overarching travel challenge was lack of transportation, yet most participants favored in-person appointments over telehealth despite driving long distances. Future research should explore patient attitudes towards telehealth in greater depth.

6.
AIDS Behav ; 27(8): 2478-2487, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-2174468

ABSTRACT

The emergence of the COVID-19 pandemic necessitated rapid expansion of telehealth as part of healthcare delivery. This study compared HIV-related no-shows by visit type (in-person; video; telephone) during the COVID-19 pandemic (April 2020-September 2021) from the Data for Care Alabama project. Using all primary care provider visits, each visit's outcome was categorized as no-show or arrived. A logistic regression model using generalized estimating equations accounting for repeat measures in individuals and within sites calculated odds ratios (OR) and their accompanying 95% confidence interval (CI) for no-shows by visit modality. The multivariable models adjusted for sociodemographic factors. In-person versus telephone visits [OR (95% CI) 1.64 (1.48-1.82)] and in-person versus video visits [OR (95% CI) 1.53 (1.25-1.85)] had higher odds of being a no-show. In-person versus telephone and video no-shows were significantly higher. This may suggest success of telehealth visits as a method for HIV care delivery even beyond COVID-19.


Subject(s)
COVID-19 , HIV Infections , Telemedicine , Humans , COVID-19/epidemiology , Pandemics , Retrospective Studies , HIV Infections/epidemiology , Alabama/epidemiology
7.
Health Promot Pract ; : 15248399221135589, 2022 Nov 30.
Article in English | MEDLINE | ID: covidwho-2138966

ABSTRACT

People experiencing homelessness are at increased risk for HIV, and people with HIV (PWH) experiencing homelessness are more likely to experience suboptimal HIV health outcomes than PWH with stable housing. Within Alabama, a state prioritized in the Ending the HIV Epidemic initiative, Jefferson County consistently has the highest number of new HIV diagnoses as well as a high percentage of the state's homeless population. To address the twin epidemics of both HIV and homelessness within the high-priority setting of Jefferson County, Alabama, this 1-year community-based project, Ending the HIV Epidemic: Addressing HIV Health and Homelessness (AH3), sought to increase HIV testing and linkage to care among this population by placing a full-time case manager trained in HIV testing and case management at a homeless shelter. Results demonstrated that HIV testing was highly acceptable: 733 individuals were offered a test, and only 2.7% (n = 20) declined. Nine previously diagnosed, out of care PWH and one newly diagnosed PWH were identified through AH3 testing efforts. Of these, five (50%) were linked to care at a local HIV clinic. The remaining five PWH left the shelter before they could be linked to care. Just 10 shelter guests expressed interest in taking PrEP (just 1.4% of guests who tested negative for HIV), and only one of these linked to PrEP care. Future health promotion programs are needed to address mental health and other ancillary needs among this population, as well as programs that provide access to PrEP and other HIV prevention services.

8.
Heliyon ; 8(7): e09887, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2004105

ABSTRACT

Galahad™ is a proanthocyanidin complexed with polysaccharides that inactivates viruses and indicates potential for an innovative approach to making protective vaccines. The polysaccharide portion of Galahad™ consists mainly of arabinan and arabinogalactan. In a seven-day toxicity study in rats, it was not toxic even when tested undiluted. Galahad™ inactivated a wide range of DNA and RNA viruses including adenoviruses, corona viruses such as SARS-CoV-2, and influenza viruses. Electron microscopy studies showed that exposure to Galahad™ caused extensive clumping of virions followed by lack of detection of virions after longer periods of exposure. Based on the viral inactivation data, the hypotheses tested is that Galahad™ inactivation of virus can be used to formulate a protective inactivated virus vaccine. To evaluate this hypothesis, infectious influenza A virus (H5N1, Duck/MN/1525/81) with a titer of 105.7 CCID50/0.1 ml was exposed for 10 min to Galahad™. This treatment caused the infectious virus titer to be reduced to below detectable limits. The Galahad™ -inactivated influenza preparation without adjuvant or preservative was given to BALB/c mice using a variety of routes of administration and dosing regimens. The most protective route of administration and dosing regimen was when mice were given the vaccine twice intranasally, the second dose coming 14 days after the primary vaccine dose. All the mice receiving this vaccine regimen survived the virus challenge while only 20% of the mice receiving placebo survived. This suggests that a Galahad™-inactivated influenza virus vaccine can elicit a protective immune response even without the use of an adjuvant. This technology should be investigated further for its potential to make effective human vaccines.

9.
Prog Community Health Partnersh ; 16(2S): 99-107, 2022.
Article in English | MEDLINE | ID: covidwho-1974218

ABSTRACT

BACKGROUND: Birmingham AIDS Outreach (BAO) is one of three study sites partnering with the University of Pittsburgh Graduate School of Public Health (Pitt Public Health) for a National Institutes of Health-funded randomized controlled trial on a financial management intervention for people with HIV who are experiencing homelessness or housing instability. After the onset of the coronavirus disease 2019 (COVID-19) pandemic in March 2020, the study team used a community-engaged approach to adapt research protocols at this site. We sought to describe a community-engaged approach to restarting National Institutes of Health-funded research during the COVID-19 pandemic. METHODS: Partners at Pitt Public Health and BAO developed a set of agency-wide COVID-19 policies and procedures for BAO organized around Rhodes' critical elements of community engagement. CONCLUSIONS: The challenges presented by COVID-19 in the research sector have provided an opportunity to reevaluate study activities and increase the extent to which research is conducted in a community-centered manner.


Subject(s)
COVID-19 , Pandemics , Community Participation , Community-Based Participatory Research , Humans , Stakeholder Participation
10.
Front Pharmacol ; 13: 891535, 2022.
Article in English | MEDLINE | ID: covidwho-1917237

ABSTRACT

Azadirachta indica (A. Juss), also known as the neem tree, has been used for millennia as a traditional remedy for a multitude of human ailments. Also recognized around the world as a broad-spectrum pesticide and fertilizer, neem has applications in agriculture and beyond. Currently, the extensive antimicrobial activities of A. indica are being explored through research in the fields of dentistry, food safety, bacteriology, mycology, virology, and parasitology. Herein, some of the most recent studies that demonstrate the potential of neem as a previously untapped source of novel therapeutics are summarized as they relate to the aforementioned research topics. Additionally, the capacity of neem extracts and compounds to act against drug-resistant and biofilm-forming organisms, both of which represent large groups of pathogens for which there are limited treatment options, are highlighted. Updated information on the phytochemistry and safety of neem-derived products are discussed as well. Although there is a growing body of exciting evidence that supports the use of A. indica as an antimicrobial, additional studies are clearly needed to determine the specific mechanisms of action, clinical efficacy, and in vivo safety of neem as a treatment for human pathogens of interest. Moreover, the various ongoing studies and the diverse properties of neem discussed herein may serve as a guide for the discovery of new antimicrobials that may exist in other herbal panaceas across the globe.

11.
Viruses ; 14(5)2022 04 21.
Article in English | MEDLINE | ID: covidwho-1855814

ABSTRACT

Although the establishment, maintenance and reactivation from alphaherpesvirus latency is far from fully understood, some things are now manifestly clear: Alphaherpesvirus latency occurs in neurons of the peripheral nervous system and control of the process is multifactorial and complex. This includes components of the immune system, contributions from non-neuronal cells surrounding neurons in ganglia, specialized nucleic acids and modifications to the viral DNA to name some of the most important. Efficacious vaccines have been developed to control both acute varicella and zoster, the outcome of reactivation, but despite considerable effort vaccines for acute herpes simplex virus (HSV) infection or reactivated lesions have thus far failed to materialize despite considerable effort. Given the relevance of the immune system to establish and maintain HSV latency, a vaccine designed to tailor the HSV response to maximize the activity of components most critical for controlling reactivated infection might limit the severity of recurrences and hence reduce viral transmission. In this review, we discuss the current understanding of immunological factors that contribute to HSV and VZV latency, identify differences between varicella-zoster virus (VZV) and HSV that could explain why vaccines have been valuable at controlling VZV disease but not HSV, and finish by outlining possible strategies for developing effective HSV vaccines.


Subject(s)
Chickenpox , Herpes Simplex , Herpes Simplex/complications , Herpesvirus 3, Human/physiology , Humans , Immune System , Twins, Dizygotic , Vaccine Efficacy
12.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.05.09.22274842

ABSTRACT

IntroductionThe COVID-19 pandemic underlined that guidelines and recommendations must be made more accessible and more understandable to the general public, including adults, parents, and youth, to improve health outcomes. The objective of this study is to evaluate, quantify, and compare the publics (youth, parents, and adult populations) understanding, usability, satisfaction, intention to implement, and preference for different ways of presenting COVID-19 health recommendations derived from the COVID-19 Living Map of Recommendations and Gateway to Contextualization (herein referred to as the RecMap). Methods and AnalysisThis is a protocol for a multi-method study. We will conduct pragmatic allocation-concealed, blinded superiority randomized controlled trials (RCT) in three populations to test alternative formats of presenting health recommendations: adults (21 years of age or older), parents (18 years or above and are a parent or legal guardian of a child under 18 years old), and youth (15 to 24 years old), with at least 240 participants in each population. The research will consist of a randomized online survey and an optional one-on-one interview. Prior to initiating the RCT, our interventions will have been refined with relevant stakeholder input. In each population group, the intervention arm will receive a plain language recommendation (PLR) format while the control arm will receive the corresponding original recommendation format as originally published by the guideline organizations (herein referred to as Standard Language Version). Our primary outcome is understanding, and our secondary outcomes are accessibility and usability, satisfaction, intended behavior, and preference for the two recommendation formats. Each populations results will be analyzed separately. However, we are planning a meta-analysis of the results across populations, and will also explore potential interaction and subgroup effects within each population. At the end of each survey, participants will be invited to participate in a one-on-one, virtual semi-structured interview to explore their user experience and their learning preferences and future research. All interviews will be transcribed and analyzed using the principles of thematic analysis and a hybrid inductive and deductive approach. Iterative member checking, triangulation, interpretation, and saturation of themes will be sought to enhance reliability. Ethics and DisseminationThrough Clinical Trials Ontario (CTO), the Hamilton Integrated Research Ethics Board has reviewed and approved this protocol (Project ID: 3856). The University of Alberta has approved the parent portion of the trial (Project ID:00114894). All potential participants will be required to provide informed consent. The findings from this study will be disseminated through open-access publications in peer-reviewed journals and using social media. Strengths and limitations of this studyO_LIWe are following a multi-method approach: randomized controlled trials and qualitative interviews. The qualitative results will supplement and help explain our quantitative findings. C_LIO_LIThis protocol is reported in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT), which enhances transparency and completeness. The trials use previously validated outcomes from similar trials. This will strengthen the credibility of our results. C_LIO_LIOur study is testing an optimized plain language recommendation format, which makes our intervention relevant to our stakeholder groups, and is recruiting internationally, which ensures the inclusion of a diverse population. Recruitment will take place online using social media, and data will be collected using an online survey. This allows for self-selection and limits accessibility to those who have no or limited digital access, which in turn limits generalizability. C_LIO_LIWhile the recommendations are offered in multiple languages through the RecMap, the study is only testing English plain language recommendation summaries. C_LI


Subject(s)
COVID-19
13.
Biomaterials ; 278: 121159, 2021 11.
Article in English | MEDLINE | ID: covidwho-1509590

ABSTRACT

The SARS-CoV-2 virus has caused an unprecedented global crisis, and curtailing its spread requires an effective vaccine which elicits a diverse and robust immune response. We have previously shown that vaccines made of a polymeric glyco-adjuvant conjugated to an antigen were effective in triggering such a response in other disease models and hypothesized that the technology could be adapted to create an effective vaccine against SARS-CoV-2. The core of the vaccine platform is the copolymer p(Man-TLR7), composed of monomers with pendant mannose or a toll-like receptor 7 (TLR7) agonist. Thus, p(Man-TLR7) is designed to target relevant antigen-presenting cells (APCs) via mannose-binding receptors and then activate TLR7 upon endocytosis. The p(Man-TLR7) construct is amenable to conjugation to protein antigens such as the Spike protein of SARS-CoV-2, yielding Spike-p(Man-TLR7). Here, we demonstrate Spike-p(Man-TLR7) vaccination elicits robust antigen-specific cellular and humoral responses in mice. In adult and elderly wild-type mice, vaccination with Spike-p(Man-TLR7) generates high and long-lasting titers of anti-Spike IgGs, with neutralizing titers exceeding levels in convalescent human serum. Interestingly, adsorbing Spike-p(Man-TLR7) to the depot-forming adjuvant alum amplified the broadly neutralizing humoral responses to levels matching those in mice vaccinated with formulations based off of clinically-approved adjuvants. Additionally, we observed an increase in germinal center B cells, antigen-specific antibody secreting cells, activated T follicular helper cells, and polyfunctional Th1-cytokine producing CD4+ and CD8+ T cells. We conclude that Spike-p(Man-TLR7) is an attractive, next-generation subunit vaccine candidate, capable of inducing durable and robust antibody and T cell responses.


Subject(s)
COVID-19 , Immunity, Humoral , Adjuvants, Immunologic , Aged , Animals , Antibodies, Neutralizing , Antibodies, Viral , CD8-Positive T-Lymphocytes , COVID-19 Vaccines , Humans , Immunity, Cellular , Mice , SARS-CoV-2
14.
Chest ; 161(3): 710-727, 2022 03.
Article in English | MEDLINE | ID: covidwho-1491838

ABSTRACT

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.


Subject(s)
COVID-19/complications , Pandemics , Respiratory Insufficiency/drug therapy , SARS-CoV-2 , Thrombosis/complications , Tissue Plasminogen Activator/administration & dosage , Adolescent , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , Cross-Sectional Studies , Female , Fibrinolytic Agents/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Partial Thromboplastin Time , Respiratory Insufficiency/blood , Respiratory Insufficiency/etiology , Retrospective Studies , Thrombosis/blood , Thrombosis/drug therapy , Treatment Outcome , Young Adult
15.
Adv Geriatr Med Res ; 3(3)2021.
Article in English | MEDLINE | ID: covidwho-1316057

ABSTRACT

As of December 2020, there were more than 900,000 COVID-19 hospitalizations in the US with about 414,000 among individuals aged 65 years and older. Recent evidence suggests a growing number of older patients continue to suffer serious neurological comorbidities including polyneuropathy, cerebrovascular disease, central nervous system infection, cognitive deficits, and fatigue following discharge. Studies suggest that complaints manifest late in disease and persist beyond resolution of acute COVID-19 symptoms. Recent research reports that neurocognitive symptoms are correlated with severe disease, older age, male gender, and comorbidities including hypertension, renal failure, and neoplastic disease. The underlying causes are unclear, but current hypotheses include hypoxic-ischemic brain injury, immunopathological mechanisms, and neurotropism of SARS-CoV-2 infection. There is a pressing need for more research into the underlying mechanisms of post-COVID-19 neurological sequela, particularly in the elderly, a population already burdened with neurocognitive disorders.

16.
J Control Release ; 335: 527-540, 2021 07 10.
Article in English | MEDLINE | ID: covidwho-1246017

ABSTRACT

Inflammation and neovascularization are key pathological events in human age-related macular degeneration (AMD). Activated microglia/macrophages (mi/ma) and retinal pigmented epithelium (RPE) play an active role in every stage of disease progression. Systemic therapies that can target these cells and address both inflammation and neovascularization will broaden the impact of existing therapies and potentially open new avenues for early AMD where there are no viable therapies. Utilizing a clinically relevant rat model of AMD that mirrors many aspects that of human AMD pathological events, we show that systemic hydroxyl-terminated polyamidoamine dendrimer-triamcinolone acetonide conjugate (D-TA) is selectively taken up by the injured mi/ma and RPE (without the need for targeting ligands). D-TA suppresses choroidal neovascularization significantly (by >80%, >50-fold better than free drug), attenuates inflammation in the choroid and retina, by limiting macrophage infiltration in the pathological area, significantly suppressing pro-inflammatory cytokines and pro-angiogenic factors, with minimal side effects to healthy ocular tissue and other organs. In ex vivo studies on human postmortem diabetic eyes, the dendrimer is also taken up into choroidal macrophages. These results suggest that the systemic hydroxyl dendrimer-drugs can offer new avenues for therapies in treating early/dry AMD and late/neovascular AMD alone, or in combination with current anti-VEGF therapies. This hydroxyl dendrimer platform but conjugated to a different drug is undergoing clinical trials for severe COVID-19, potentially paving the way for faster clinical translation of similar compounds for ocular and retinal disorders.


Subject(s)
COVID-19 , Dendrimers , Wet Macular Degeneration , Angiogenesis Inhibitors , Animals , Choroid , Humans , Inflammation/drug therapy , Rats , SARS-CoV-2 , Vascular Endothelial Growth Factor A , Visual Acuity
17.
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.05.20.445060

ABSTRACT

The SARS-CoV-2 virus has caused an unprecedented global crisis, and curtailing its spread requires an effective vaccine which elicits a diverse and robust immune response. We have previously shown that vaccines made of a polymeric glyco-adjuvant conjugated to an antigen were effective in triggering such a response in other disease models and hypothesized that the technology could be adapted to create an effective vaccine against SARS-CoV-2. The core of the vaccine platform is the copolymer p(Man-TLR7), composed of monomers with pendant mannose or a toll-like receptor 7 (TLR7) agonist. Thus, p(Man-TLR7) is designed to target relevant antigen-presenting cells (APCs) via mannose-binding receptors and then activate TLR7 upon endocytosis. The p(Man-TLR7) construct is amenable to conjugation to protein antigens such as the Spike protein of SARS-CoV-2, yielding Spike-p(Man-TLR7). Here, we demonstrate Spike-p(Man-TLR7) vaccination elicits robust antigen-specific cellular and humoral responses in mice. In adult and elderly wild-type mice, vaccination with Spike-p(Man-TLR7) generates high and long-lasting titers of anti-Spike IgGs, with neutralizing titers exceeding levels in convalescent human serum. Interestingly, adsorbing Spike-p(Man-TLR7) to the depot-forming adjuvant alum, amplified the broadly neutralizing humoral responses to levels matching those in mice vaccinated with formulations based off of clinically-approved adjuvants. Additionally, we observed an increase in germinal center B cells, antigen-specific antibody secreting cells, activated T follicular helper cells, and polyfunctional Th1-cytokine producing CD4+ and CD8+ T cells. We conclude that Spike-p(Man-TLR7) is an attractive, next-generation subunit vaccine candidate, capable of inducing durable and robust antibody and T cell responses.

19.
Prev Med ; 144: 106399, 2021 03.
Article in English | MEDLINE | ID: covidwho-1139631

ABSTRACT

WHO/UNICEF estimates for HPV vaccination coverage from 2010 to 2019 are analyzed against the backdrop of the 90% coverage target for HPV vaccination by 2030 set in the recently approved global strategy for cervical cancer elimination as a public health problem. As of June 2020, 107 (55%) of the 194 WHO Member States have introduced HPV vaccination. The Americas and Europe are by far the WHO regions with the most introductions, 85% and 77% of their countries having already introduced respectively. A record number of introductions was observed in 2019, most of which in low- and middle- income countries (LMIC) where access has been limited. Programs had an average performance coverage of around 67% for the first dose and 53% for the final dose of HPV. LMICs performed on average better than high- income countries for the first dose, but worse for the last dose due to higher dropout. Only 5 (6%) countries achieved coverages with the final dose of more than 90%, 22 countries (21%) achieved coverages of 75% or higher while 35 (40%) had a final dose coverage of 50% or less. When expressed as world population coverage (i.e., weighted by population size), global coverage of the final HPV dose for 2019 is estimated at 15%. There is a long way to go to meet the 2030 elimination target of 90%. In the post-COVID era attention should be paid to maintain the pace of introductions, specially ensuring the most populous countries introduce, and further improving program performance globally.


Subject(s)
COVID-19 , Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Europe , Female , Humans , Immunization Programs , Papillomavirus Infections/prevention & control , SARS-CoV-2 , United Nations , Uterine Cervical Neoplasms/prevention & control , Vaccination , Vaccination Coverage , World Health Organization
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