Background: During pregnancy, mothers and their infants are at increased risk for complications due to COVID-19 infection, influenza, and pertussis. At the time of writing, the previous advisory committee on immunization practices (ACIP) recommended that pregnant women receive the COVID-19 vaccine, influenza, tetanus-toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine, as well as respiratory syncytial virus vaccinations during pregnancy. The COVID-19 pandemic greatly impacted routine vaccinations especially among medically underserved women in the South. The barriers to recommended vaccinations during pregnancy for medically underserved women in the South are unclear and require further investigation. The purpose of this study is to examine the attitudes, opinions, and beliefs of a multiracial pregnant cohort from diverse backgrounds in Central Tennessee about their experiences with the vaccines that are recommended during pregnancy. The vaccines included in the study are COVID-19, flu, and Tdap because RSV was not yet FDA-approved for pregnant women at the launch of this study. Methods: In this study, we focus on medically underserved women in Nashville, Tennessee, and the surrounding rural counties regarding vaccine acceptance and initiation of the COVID-19, influenza, and the Tdap vaccines. This study involved 208 pregnant people (100%) aged 18–49 years. All respondents were pregnant at the time of the study. The study consisted of a 26 question Redcap survey about participants’ beliefs, attitudes, opinions, and experiences with the COVID-19, flu, and Tdap vaccines during their pregnancy. Results: The randomly selected participants in the cohort were 40.4% White, 31.7% Black, 21.6% Hispanic, and 6.3% other race/ethnicity. The mothers in the cohort were young, with an average age of 27 years, most were married, and 52.8% had an annual household income before taxes of less than USD 35,000. Only 19.2% of the mothers in this study were very confident of the safety of the COVID-19 vaccine, compared to 32.7% for both the flu and Tdap vaccines. Overall, primary care providers were identified as the most trusted messengers for both disease and vaccine information for COVID-19, flu, and Tdap. However, only 11 participants out of 208 received all three of the ACIP recommended vaccines during their pregnancies in the study, barring the time-dependent vaccination for Tdap. The most common reasons for not receiving these vaccines involved concerns for the safety of themselves and their babies and a fear of needles. Conclusions: Education and awareness of ACIP-recommended vaccines during pregnancy needs improvement, and the support of primary care providers as the main driver of pregnancy vaccine initiation is essential.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and the world. Infection with high-risk oncogenic HPV strains has been shown to induce cellular transformation leading to anogenital and oropharyngeal cancers. The HPV vaccine, first developed in 2006 for females aged 9–26 years, has been demonstrated to be safe and effective in preventing 90% of all HPV-associated cancers. However, vaccine hesitancy, misinformation, and barriers to vaccine access has resulted in suboptimal vaccination rates among adolescent populations, especially in rural communities in the South. HPV vaccine coverage in Tennessee is currently below the national average and below the Healthy People 2030 goal of an 80% vaccination rate for individuals 13–17 years old based on recommendation guidelines for up-to-date HPV vaccination status as of 2022. HPV vaccination rates for Tennesseans with private insurance in 2022 were 68% and 38% for those that were uninsured. Up-to-date HPV vaccination rates in 2022 for Tennesseans were 58% and 46% for those living in urban communities and rural communities, respectively. Overall, HPV-associated cancers rates are higher in Tennessee, at 12.9/100,000 compared to the overall rate in the US of 11.8/100,000 persons in 2022. Interventions to improve HPV vaccine awareness, education, and access could improve vaccine confidence and uptake, especially among rural and uninsured populations in Tennessee. Most recently, the Advisory Committee on Immunization Practices (ACIP) expanded recommendations for HPV vaccinations for some individuals aged 27–45 years who were not vaccinated at a younger age, with shared clinical decision making. Further research is needed to evaluate the impact of this recommendation on HPV vaccination rates and cancer prevention in Tennessee.

Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol sequestering agent that has been explored as a potential antiviral drug against enveloped viruses and is currently under clinical investigation for Niemann Pick C disease. We previously demonstrated that HP-BCD inhibits SARS-CoV-2 replication and infectivity by targeting both host cells and viral particles. In this study, we investigated the molecular mechanisms underlying HP-BCD antiviral activity against SARS-CoV-2 in vitro. Treatment of Vero cells with HP-BCD altered intracellular compartmentalization, as indicated by the redistribution of early endosome markers. Also, HP-BCD treatment prior to SARS-CoV-2 inoculation promoted an accumulation of nucleocapsid protein at early time points after infection. Infected cells pretreated with HP-BCD exhibited reduced cholesterol and lipid droplets content, potentially hampering the formation of new double-membrane vesicles. Consistently, viral replication complexes were scarcely detected in treated cells, which displayed disformed vesicle-like structures and lacked membrane-associated virus particles. Notably, HP-BCD also reduced viral replication when administered after virus adsorption, although with lower efficacy, indicating interference with potentially multiple stages of the SARS-CoV-2 life cycle. These findings suggest that HP-BCD effectively impairs SARS-CoV-2 biosynthesis through multiple mechanisms with minimal cytotoxicity, supporting its potential as a promising antiviral candidate.

The aberrant expression of α defensin 5 (DEFA5) protein in colonic inflammatory bowel diseases (IBDs) underlies the distinct pathogenesis of Crohn’s colitis (CC). It can serve as a biomarker for differentiating CC from Ulcerative colitis (UC), particularly in Indeterminate colitis (IC) cases into UC and CC. We evaluated the specificity of commercially available anti-DEFA5 antibodies, emphasizing the need to further validate their appropriateness for a given application and highlighting the necessity for novel antibodies. We established two mice monoclonal DEFA5 antibody clones, 1A8 and 4F5, by immunizing mice with purified recombinant protein. We validated the specificity, sensitivity, and cross-reactivity of these antibodies in recognizing both endogenous and recombinant DEFA5 protein, especially for use in Immunohistochemistry (IHC), Western blot (WB), Immunoprecipitation (IP), and enzyme-linked immunosorbent assay (ELISA). Clones 1A8 and 4F5 effectively recognized the endogenous DEFA5 in active human colon tissue from patients with diverticulitis (DV), UC, CC, and IC disease samples, as well as in transiently transfected HEK293T cells expressing DEFA5 with minimal non-confounding cross reactivity. The 1A8 and 4F5 clones are useful for a wide variety of immunoassays, including WB, IHC, IP/WB, and ELISA. Their specificity enhances their potential as valuable tools for research applications in IBD colitis.

The Biden administration decided to end the COVID-19 National and Public Health emergencies on May 11, 2023. These emergency declarations were established by the Trump Administration in early 2020. Under the COVID-19 emergency declarations, US citizens were provided with COVID-19 testing, vaccines, and treatments at little or no cost. The declarations allowed the federal government the option of waiving and or modifying government programs such Medicare, Medicaid. The emergency declarations were directly tied to other COVID-19 related provisions that have also expired that includes Economic Security (CARES) Act, the American Rescue Plan Act (ARPA), the Families First Coronavirus Response Act (FFCRA), the Coronavirus Aid, Relief, and the Inflation Reduction Act (IRA), the Consolidated Appropriations Act, 2023 (CAA). In addition, there were other federal and state emergency programs that were provided and too numerous to report here. At the time of this writing, the state of Tennessee continues to have moderate and sporadic spikes in COVID-19 cases and hospitalizations. Tennessee has higher than the national average of uninsured and underinsured people in the US. In Tennessee, more than 600,000 people are uninsured or underinsured in 2023 according to a study by the Kaiser Family Foundation. The ending of the PHE greatly impact coverage, cost, and access to COVID related services that will disproportionately affect the uninsured and medically underserved populations in Tennessee, the south in general, and throughout the US. Medically underserved populations are those groups with disparities in primary care, living in poverty, older, or having higher than expected infant mortality.

Health equity is the state in which everyone has fair and just opportunities to attain their highest level of health. The field of human genomics has fallen short in increasing health equity, largely because the diversity of the human population has been inadequately reflected among participants of genomics research. This lack of diversity leads to disparities that can have scientific and clinical consequences. Achieving health equity related to genomics will require greater effort in addressing inequities within the field. As part of the commitment of the National Human Genome Research Institute (NHGRI) to advancing health equity, it convened experts in genomics and health equity research to make recommendations and performed a review of current literature to identify the landscape of gaps and opportunities at the interface between human genomics and health equity research. This Perspective describes these findings and examines health equity within the context of human genomics and genomic medicine. This Perspective discusses how addressing disparities in genomics can drive improvements in health equity more broadly.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and the world. Infection with high-risk oncogenic HPV strains have been shown to induce cellular transformation leading to anogenital and oropharyngeal cancers. The HPV vaccine first developed in 2006 for females aged 9-26 years has been demonstrated to be safe and effective in preventing 90% of all HPV associated cancers. However, vaccine hesitancy, misinformation, and barriers to vaccine access has resulted in suboptimal vaccination rates among adolescent populations, especially in rural communities in the South. HPV vaccine coverage in Tennessee is currently below the national average and below the Healthy People 2030 goal of an 80% vaccination rate for individuals 13-17 years old based on recommendation guidelines for up-to-date HPV vaccination status as of 2022. HPV vaccination rates for Tennesseans with private insurance in 2022 was 68% and 38% for those that were insured. Up-to-date HPV vaccination rates for Tennesseans living in urban communities was 58% in 2022 and 46% for those living in rural communities. Overall, HPV associated cancers rates are higher in Tennessee at 12.9/100,000 compared to the overall rate in the US of 11.8/100,000 persons in 2022. Interventions to improve HPV vaccine awareness, education, and access could improve vaccine confidence and uptake especially among rural and uninsured populations in Tennessee. Most recently, the Advisory Committee on Immunization Practices (ACIP) has expanded recommendations for the HPV vaccinations for some individuals 27-45 years who were not vaccinated at a younger age with shared clinical decision-making. The impact of this recommendation on Tennesseans should be examined.

Background Robust evidence suggests that the aberrant expression of α defensin 5 protein (DEFA5) in colon inflammatory bowel diseases (IBDs) underlies the distinct pathogenesis of Crohn’s colitis, can be exploited as a reliable diagnostic biomarker to differential diagnosis of Crohn’s colitis (CC) from Ulcerative colitis (UC) in otherwise indeterminate colitis (IC). We evaluated the specificity of the commercially available anti-DEFA5 antibodies and showed further validation of their appropriateness for a given application is required. Methods We established two mouse monoclonal DEFA5 antibody clones 1A8 and 4F5 by immunizing the mice with purified recombinant protein and validated the specificity, selectivity and cross reactivity in recognizing the endogenous and recombinant DEFA5 protein, especially for Immunohistochemistry, Western blot, Immunoprecipitation, or enzyme-linked immunosorbent assay. Results Clones 1A8 and 4F5 recognized effectively the endogenous DEFA5 in active human diverticulitis (DV), UC, CC or IC disease samples, including transiently transfected HEK293T cells expressing DEFA5 with high degree of specificity and minimal non-confounding cross reactivity. Conclusions 1A8 and 4F5 clones are worth studying in larger IBD cohorts to fully address whether DEFA5 expression may be used as a diagnostic biomarker to discrimination of the diagnosis of UC from CC or IC into authentic CC or UC or a colitis with different pathological characteristics.

Background: The Southern region of the United States has the highest HIV incidence, and new infections disproportionately affect Black Americans. The Tennessee Center for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI) program supports the training of individuals from groups underrepresented in medicine and science in multiple areas of research to increase the pool of HIV-focused investigators at early educational and career stages. Setting: The Tennessee CFAR is a partnership between Vanderbilt University Medical Center, Meharry Medical College (one of the oldest historically Black medical colleges), Tennessee Department of Health, and Nashville Community AIDS Resources, Education and Services (a sophisticated community service organization, which emphasizes research training responsive to regional and national priorities). Methods: The Tennessee CFAR CDEIPI program leverages existing Vanderbilt University Medical Center and Meharry Medical College structured biomedical training programs for high school and undergraduate students to provide an intensive, mentored, HIV research experience augmented by CFAR resources situating this training within the broader history, scientific breadth, and societal and political aspects of the HIV epidemic. Results: The first year of the Tennessee CFAR CDEIPI program trained 3 high school and 3 undergraduate students from underrepresented in medicine and science backgrounds in basic, clinical/translational, and community-focused research projects with a diverse group of 9 mentors. All students completed the program, and evaluations yielded positive feedback regarding mentoring quality and effectiveness, and continued interest in HIV-related research. Conclusions: The Tennessee CFAR CDEIPI program will continue to build upon experience from the first year to further contribute to national efforts to increase diversity in HIV-related research.

COVID-19 vaccine hesitancy and uptake among Southern states in the US has been problematic throughout the pandemic. To characterize COVID-19 vaccine hesitancy and uptake among medically underserved communities in Tennessee. We surveyed 1482 individuals targeting minority communities in Tennessee from 2 October 2021 to 22 June 2022. Participants who indicated that they did not plan to receive or were unsure whether to receive the COVID-19 vaccine were considered vaccine-hesitant. Among participants, 79% had been vaccinated, with roughly 5.4% not likely at all to be vaccinated in the next three months from the date that the survey was conducted. When focusing particularly on Black/AA people and white people, our survey results revealed a significant association between race (Black/AA, white, or people of mixed Black/white ancestry) and vaccination status (vaccinated or unvaccinated) (p-value = 0.013). Approximately 79.1% of all participants received at least one dose of a COVID-19 vaccine. Individuals who were concerned with personal/family/community safety and/or wanted a return to normalcy were less likely to be hesitant. The study found that the major reasons cited for refusing the COVID-19 vaccines were distrust in vaccine safety, concerns about side effects, fear of needles, and vaccine efficacy.

The COVID-19 Omicron variant and its subvariants are now the dominant variants circulating in the US. Therefore, the original COVID-19 vaccine cannot offer full protection. Instead, vaccines that target the spike proteins of the Omicron variants are warranted. Hence, the FDA recommended the development of a bivalent booster. Unfortunately, despite the safety and immunogenicity of the Omicron bivalent boosters from Pfizer and Moderna, uptake in the US has been poor. At this time, only 15.8% of individuals in the US aged five and older have received the Omicron bivalent booster (OBB). The rate is 18% for those aged 18 and older. Poor vaccine confidence and booster uptake are often fueled by misinformation and vaccine fatigue. These result in more problems associated with vaccine hesitancy, which are particular prevalent in Southern states in the US. In Tennessee, the OBB vaccination rate for eligible recipients is only 5.88% at time of writing (16 February 2023). In this review, we discuss (1) the rationale for developing the OBBs; (2) the efficacy and safety of the bivalent boosters; (3) the adverse events associated with these boosters; (4) vaccine hesitancy associated with the OBBs uptake in Tennessee; (5) implications for vulnerable populations, disparities in uptake of OBBs in Tennessee, and strategies to improve vaccine confidence and OBB uptake. In support of public health, it is essential that we continue to provide education, awareness, and vaccine access to the vulnerable and medically underserved populations in Tennessee. Receiving the OBBs is the most effective method to date of protecting the public against severe COVID disease, hospitalization, and death.

The American College of Obstetricians and Gynecologists (AGOG) recommends the FDA-approved Pfizer and Moderna mRNA COVID-19 vaccines and boosters for all eligible pregnant women in the US. However, COVID-19 vaccine confidence and uptake among pregnant minority women have been poor. While the underlying reasons are unclear, they are likely to be associated with myths and misinformation about the vaccines. Direct and indirect factors that deter minority mothers in the US from receiving the mRNA COVID-19 vaccines require further investigation. Here, we examine the historical perspectives on vaccinations during pregnancy. We will examine the following aspects: (1) the influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccinations during pregnancy; (2) the exclusion of pregnant and lactating women from COVID-19 vaccine trials; (3) COVID-19 vaccine safety during pregnancy, obstetric complications associated with symptomatic COVID-19 during pregnancy, COVID-19 vaccine hesitancy among pregnant minority women, and racial disparities experienced by pregnant minority women due to the COVID-19 pandemic as well as their potential impact on pregnancy care; and (4) strategies to improve COVID-19 vaccine confidence and uptake among pregnant minority women in the US. COVID-19 vaccine hesitancy among minority mothers can be mitigated by community engagement efforts that focus on COVID-19 vaccine education, awareness campaigns by trusted entities, and COVID-19-appropriate perinatal counseling aimed to improve COVID-19 vaccine confidence and uptake.

The incidence of COVID-19 breakthrough infections-an infection that occurs after you have been vaccinated-has increased in frequency since the Delta and now Omicron variants of the SARS-CoV-2 coronavirus have become the dominant strains transmitted in the United States (US). Evidence suggests that individuals with breakthrough infections, though rare and expected, may readily transmit COVID-19 to unvaccinated populations, posing a continuing threat to the unvaccinated. Here, we examine factors contributing to breakthrough infections including a poor immune response to the vaccines due to the fact of advanced age and underlying comorbidities, the natural waning of immune protection from the vaccines over time, and viral variants that escape existing immune protection from the vaccines. The rise in breakthrough infections in the US and how they contribute to new infections, specifically among the unvaccinated and individuals with compromised immune systems, will create the need for additional booster vaccinations or development of modified vaccines that directly target current variants circulating among the general population. The need to expedite vaccination among the more than 49.8 million unvaccinated eligible people in the US is critical.

COVID-19 is marked by extensive damage to the respiratory system, often accompanied by systemic manifestations, due to both viral cytopathic effects and hyperinflammatory syndrome. Therefore, the development of new therapeutic strategies or drug repurposing aiming to control virus replication and inflammation are required to mitigate the impact of the disease. Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol-sequestering agent with antiviral activity that has been demonstrated against enveloped viruses in in vitro and in vivo experimental models. We also demonstrated that HP-BCD has an immunomodulatory effect, inhibiting the production of selected proinflammatory cytokines induced by microbial products. Importantly, this drug has been used in humans for decades as an excipient in drug delivery systems and as a therapeutic agent in the treatment of Niemann pick C disease. The safety profile for this compound is well established. Here, we investigated whether HP-BCD would affect SARS-CoV-2 replication and virus-induced inflammatory response, using established cell lines and primary human cells. Treating virus or cells with HP-BCD significantly inhibited SARS-CoV-2 replication with a high selective index. A broad activity against distinct SARS-CoV-2 variants was evidenced by a remarkable reduction in the release of infectious particles. The drug did not alter ACE2 surface expression, but affected cholesterol accumulation into intracellular replication complexes, lowering virus RNA and protein levels, and reducing virus-induced cytopathic effects. Virus replication was also impaired by HP-BCD in Calu-3 pulmonary cell line and human primary monocytes, in which not only the virus, but also the production of proinflammatory cytokines were significantly inhibited. Given the pathophysiology of COVID-19 disease, these data indicate that the use HP-BCD, which inhibits both SARS-CoV2 replication and production of proinflammatory cytokines, as a potential COVID-19 therapeutic warrants further investigation.

Medroxyprogesterone acetate (MPA) is one of the most widely used contraceptives in the world. Epidemiologic studies have uncovered a possible link between the use of MPA and an increased risk of HIV-1 transmission. However, the understanding of the mechanism is still limited. Our previous publication demonstrated that the lysosomal activity in human vaginal epithelial cells attenuated the trafficking of viral particles during HIV-1 transcytosis. In this study, we show that treating human primary cervical epithelial cells with MPA led to a reduction in lysosomal activity. This reduction caused an increase in the intracellular HIV-1 accumulation and, consequently, an increase in viral release. Our study uncovers a novel mechanism by which MPA enhances HIV-1 release in primary cervical epithelial cells, thus providing vital information for HIV intervention and prevention.

There has been a continuous underrepresentation of minorities in healthcare research and vaccine trials, along with long-standing systemic racism and discrimination that have been fueling the distrust of the healthcare system among these communities for decades. The history and legacy of racial injustices and negative experiences within a culturally insensitive healthcare system have greatly contributed to vaccine hesitancy among ethnic minorities. COVID-19 vaccine hesitancy will impact vaccine uptake in the US, subsequently hindering the establishment of herd immunity (75–85% of the population vaccinated) to mitigate SARS-CoV-2 infection and transmission. Information targeting underserved racial/ethnic minorities in the US in a culturally competent manner has been lacking. This information is crucial for educating these communities about COVID-19 vaccines and their distribution as well as dispelling misinformation regarding vaccine trials, safety, and efficacy. This lack of education has greatly contributed to COVID-19 vaccine hesitancy and will increase disparities in vaccine uptake. Moreover, timely vaccinations are also essential to curtailing virus transmission and the emergence of SARS-CoV-2 variants that may evade the immune response produced by the three existing COVID-19 vaccines.

Therapeutic modalities designed specifically to inhibit COVID-19 infection and replication would limit progressive COVID-19-associated pulmonary disease in infected patients and prevent or limit systemic disease. If effective, antivirals could reduce viral transmission rates by reducing viral burden and allow time for immune clearance. For individuals infected with acute-stage disease, antivirals in support of the existing vaccines could reduce COVID-19 hospitalizations and deaths. Here, we evaluate MRCV-19, a phosphorodiamidate morpholino oligo with delivery dendrimer (Vivo-Morpholino), to prevent coronavirus infection in a cell culture model. This is a novel antiviral that effectively inhibits SARS-CoV-2 replication in vitro. By design, MRCV-19 targets the SARS-CoV-2 5’UTR and overlaps the pp1a start site of translation in order to block access of the translation initiation complex to the start. MRCV-19 testing is conducted in a high-throughput, 384-well plate format with a 10-point dose-response curve (common ratio of 2) assayed in duplicate with parallel cytotoxicity evaluations. MRCV-19 was shown to be more effective than hydroxychloroquine and remdesivir in our CPE reduction assay with low toxicity. The clinical translational impact of this study is providing the basis for evaluating MRCV-19 on a large scale in an appropriate infection model for toxicity and systemic high-level inhibition of SARS-CoV-2, which could lead in time to phase I testing in humans.

The JC polyomavirus (JCPyV/JCV) is a member of the Polyomaviridae family and is ubiquitious in the general population, infecting 50–80% of individuals globally. A primary infection with JCV usally results in an asymptomatic, persistent infection that establishes latency in the renourinary tract. Reactivation from latency via iatrogenic immununosuppression for allograft transplantation may result in organ pathology and a potential life-threatening neuropathological disease in the form of progressive multifocal leukoencephalopathy (PML). Currently, no treatment exists for PML, a rare complication that occurs after transplantation, with an incidence of 1.24 per 1000 persons a year among solid organ transplant patients. PML is also observed in HIV patients who are immununosuppressed and are not receiving antiretroviral therapy, as well as individuals treated with biologics to suppress chronic inflammatory responses due to multiple sclerosis, Crohn’s disease, non-Hodgkin’s lymphoma, rheumatoid arthritis, and other autoimmune-mediated hematological disorders. Here, we describe the proposed mechanisms of JCV reactivation as it relates to iatrogenic immunosuppression for graft survival and the treatment of proinflammatory disease, such as biologics, proposed trafficking of JCV from the renourinary tract, JCV central nervous system dissemination and the pathology of PML in immunosuppressed patients, and potential novel therapeutics for PML disease.