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Molecular Therapy : the Journal of the... May 2024Human T cell leukemia/T-lymphotropic virus type 1 (HTLV-1) infection occurs by cell-to-cell transmission and can induce fatal adult T cell leukemia. Vaccine...
Human T cell leukemia/T-lymphotropic virus type 1 (HTLV-1) infection occurs by cell-to-cell transmission and can induce fatal adult T cell leukemia. Vaccine development is critical for the control of HTLV-1 transmission. However, determining whether vaccine-induced anti-Env antibodies can prevent cell-to-cell HTLV-1 transmission is challenging. Here, we examined the protective efficacy of a vaccine inducing anti-Env antibodies against HTLV-1 challenge in cynomolgus macaques. Eight of 10 vaccinated macaques produced anti-HTLV-1 neutralizing antibodies (NAbs) and were protected from an intravenous challenge with 10 HTLV-1-producing cells. In contrast, the 2 vaccinated macaques without NAb induction and 10 unvaccinated controls showed HTLV-1 infection with detectable proviral load after challenge. Five of the eight protected macaques were administered with an anti-CD8 monoclonal antibody, but proviruses remained undetectable and no increase in anti-HTLV-1 antibodies was observed even after CD8 cell depletion in three of them. Analysis of Env-specific T cell responses did not suggest involvement of vaccine-induced Env-specific T cell responses in the protection. These results indicate that anti-Env antibody induction by vaccination can result in functionally sterile HTLV-1 protection, implying the rationale for strategies aimed at anti-Env antibody induction in prophylactic HTLV-1 vaccine development.
PubMed: 38734900
DOI: 10.1016/j.ymthe.2024.05.020 -
Nature Communications May 2024An effective HIV-1 vaccine must elicit broadly neutralizing antibodies (bnAbs) against highly diverse Envelope glycoproteins (Env). Since Env with the longest...
An effective HIV-1 vaccine must elicit broadly neutralizing antibodies (bnAbs) against highly diverse Envelope glycoproteins (Env). Since Env with the longest hypervariable (HV) loops is more resistant to the cognate bnAbs than Env with shorter HV loops, we redesigned hypervariable loops for updated Env consensus sequences of subtypes B and C and CRF01_AE. Using modeling with AlphaFold2, we reduced the length of V1, V2, and V5 HV loops while maintaining the integrity of the Env structure and glycan shield, and modified the V4 HV loop. Spacers are designed to limit strain-specific targeting. All updated Env are infectious as pseudoviruses. Preliminary structural characterization suggests that the modified HV loops have a limited impact on Env's conformation. Binding assays show improved binding to modified subtype B and CRF01_AE Env but not to subtype C Env. Neutralization assays show increases in sensitivity to bnAbs, although not always consistently across clades. Strikingly, the HV loop modification renders the resistant CRF01_AE Env sensitive to 10-1074 despite the absence of a glycan at N332.
Topics: HIV-1; Humans; env Gene Products, Human Immunodeficiency Virus; HIV Antibodies; Antibodies, Neutralizing; AIDS Vaccines; Neutralization Tests; HEK293 Cells; Consensus Sequence; HIV Infections; Protein Binding; Epitopes
PubMed: 38724518
DOI: 10.1038/s41467-024-48139-x -
BioRxiv : the Preprint Server For... Apr 2024Single-cell spatial transcriptomics promises a highly detailed view of a cell's transcriptional state and microenvironment, yet inaccurate cell segmentation can render...
Single-cell spatial transcriptomics promises a highly detailed view of a cell's transcriptional state and microenvironment, yet inaccurate cell segmentation can render this data murky by misattributing large numbers of transcripts to nearby cells or conjuring nonexistent cells. We adopt methods from ab initio cell simulation to rapidly infer morphologically plausible cell boundaries that preserve cell type heterogeneity. Benchmarking applied to datasets generated by three commercial platforms show superior performance and computational efficiency of this approach compared with existing methods. We show that improved accuracy in cell segmentation aids greatly in detection of difficult to accurately segment tumor infiltrating immune cells such as neutrophils and T cells. Lastly, through improvements in our ability to delineate subsets of tumor infiltrating T cells, we show that CXCL13-expressing CD8+ T cells tend to be more closely associated with tumor cells than their CXCL13-negative counterparts in data generated from renal cell carcinoma patient samples. Proseg is available under at open source license at https://github.com/dcjones/proseg.
PubMed: 38712065
DOI: 10.1101/2024.04.25.591218 -
Influenza and Other Respiratory Viruses May 2024Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to... (Comparative Study)
Comparative Study
BACKGROUND
Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273.
METHODS
We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers.
RESULTS
Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization.
CONCLUSION
The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1.
Topics: Humans; BNT162 Vaccine; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; Male; Immunization, Secondary; Immunoglobulin G; Female; SARS-CoV-2; Adult; 2019-nCoV Vaccine mRNA-1273; Middle Aged; Immunoglobulin A; COVID-19 Vaccines; Young Adult; Follow-Up Studies; Vaccination; Aged; Immunogenicity, Vaccine; Antibody Formation; ChAdOx1 nCoV-19; Spike Glycoprotein, Coronavirus
PubMed: 38706402
DOI: 10.1111/irv.13290 -
JAMA Network Open May 2024Pregnancy represents a window of opportunity for vaccination due to established maternal and fetal benefits of vaccination. Little is known about receipt of routinely...
IMPORTANCE
Pregnancy represents a window of opportunity for vaccination due to established maternal and fetal benefits of vaccination. Little is known about receipt of routinely recommended vaccines in pregnancy, specifically tetanus, diphtheria, plus acellular pertussis (Tdap) and influenza, among pregnant people living with HIV (PLHIV).
OBJECTIVE
To estimate prevalence of vaccination receipt among pregnant people with HIV (PLHIV) and identify demographic and clinical characteristics associated with vaccination.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter cohort study included women participating in Women's Health Study (WHS) of the Surveillance Monitoring for ART Toxicities (SMARTT) Study of the Pediatric HIV/AIDS Cohort Study. The network has been enrolling pregnant PLHIV at 22 US sites since 2007. Participants for this study enrolled between December 2017 and July 2019. Data analysis was conducted from October 2021 to March 2022.
EXPOSURE
Data on vaccination in pregnancy were collected through medical record abstraction.
MAIN OUTCOMES AND MEASURES
Vaccination receipt was defined as Tdap vaccination received at less than 36 weeks' gestation and influenza vaccination at any gestational age, based on current guidelines. Log-binomial and modified Poisson regression models with generalized estimating equations were fit to identify factors associated with successful receipt of (1) Tdap, (2) influenza, and (3) both vaccinations.
RESULTS
A total of 310 pregnancies among 278 people participating in the WHS were included (mean [SD] age, 29.5 [6.1] years; 220 [71%] Black, 77 [25%] Hispanic, and 77 [25%] race and ethnicity other than Black; 64 [21%] with perinatally acquired HIV). Less than one-third of pregnancies were vaccinated as recommended (Tdap, 32.6% [95% CI, 27.4%-38.1%]; influenza, 31.6% [95% CI, 26.5%-37.1%]; both, 22.6% [95% CI, 18.0%-27.6%]). People living with perinatally acquired HIV, those who did not identify as Black, or those who were multiparous had adjusted risk ratios (aRRs) less than 1, while older PLHIV had aRRs greater than 1, but these differences did not reach statistical significance (perinatally acquired HIV: adjusted risk ratio [aRR], 0.46; 95% CI, 0.21-1.02; race other than Black: aRR, 0.53; 95% CI, 0.26-1.08; multiparous: aRR, 0.59; 95% CI, 0.35-1.00; age 24-29 years: aRR, 2.03; 95% CI, 0.92-4.48).
CONCLUSIONS AND RELEVANCE
In this diverse, multicenter cohort of pregnant PLHIV, receipt of recommended vaccinations was low. Identifying and addressing barriers to vaccination receipt is urgently needed for pregnant people with HIV.
Topics: Humans; Female; Pregnancy; Adult; HIV Infections; United States; Pregnancy Complications, Infectious; Vaccination; Diphtheria-Tetanus-acellular Pertussis Vaccines; Influenza Vaccines; Cohort Studies; Influenza, Human; Young Adult
PubMed: 38696165
DOI: 10.1001/jamanetworkopen.2024.9531 -
Nature Medicine Jun 2024It is unclear how great a challenge pandemic and vaccine fatigue present to public health. We assessed perspectives on coronavirus disease 2019 (COVID-19) and routine...
It is unclear how great a challenge pandemic and vaccine fatigue present to public health. We assessed perspectives on coronavirus disease 2019 (COVID-19) and routine immunization as well as trust in pandemic information sources and future pandemic preparedness in a survey of 23,000 adults in 23 countries in October 2023. The participants reported a lower intent to get a COVID-19 booster vaccine in 2023 (71.6%), compared with 2022 (87.9%). A total of 60.8% expressed being more willing to get vaccinated for diseases other than COVID-19 as a result of their experience during the pandemic, while 23.1% reported being less willing. Trust in 11 selected sources of vaccine information each averaged less than 7 on a 10-point scale with one's own doctor or nurse and the World Health Organization, averaging a 6.9 and 6.5, respectively. Our findings emphasize that vaccine hesitancy and trust challenges remain for public health practitioners, underscoring the need for targeted, culturally sensitive health communication strategies.
Topics: Humans; COVID-19; Trust; Adult; COVID-19 Vaccines; Male; Female; Middle Aged; Pandemics; SARS-CoV-2; Vaccination Hesitancy; Immunization; Surveys and Questionnaires; Vaccination; Young Adult; Aged; Adolescent; Pandemic Preparedness; Information Sources
PubMed: 38684861
DOI: 10.1038/s41591-024-02939-2 -
NPJ Vaccines Apr 2024On 27–29 of September 2022, Wellcome convened an international multi-stakeholder workshop to discuss the use of Correlates of Protection (CoP) to accelerate vaccine...
On 27–29 of September 2022, Wellcome convened an international multi-stakeholder workshop to discuss the use of Correlates of Protection (CoP) to accelerate vaccine development, the hybrid format meeting was attended by 80 delegates including developers, manufacturers, regulators, public health officials and policy-makers from 17 countries, including 7 LMIC’s.
PubMed: 38684704
DOI: 10.1038/s41541-024-00872-6 -
Cureus Mar 2024Since 1997, the World Health Organization (WHO) publishes the Global Tuberculosis Report every year, which contains the most up-to-date and accurate statistical data on...
Since 1997, the World Health Organization (WHO) publishes the Global Tuberculosis Report every year, which contains the most up-to-date and accurate statistical data on tuberculosis (TB) worldwide. TB is an infectious disease that is one of the leading causes of human morbidity. It ranks among the top 10 most common causes of death worldwide and is more likely than other pathogens, such as the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), to result in a fatal outcome. After the introduction of the TB vaccine, the situation improved significantly, but the disease was not defeated. In this context, we present the clinical case of a male patient who was admitted to the Emergency Department (ED) due to a productive cough, dyspnea, and weight loss. After a complementary study, he was diagnosed with extensive diffuse pulmonary TB with a bacterial infection.
PubMed: 38681350
DOI: 10.7759/cureus.57067 -
The Pan African Medical Journal 2024Nigeria offers universal hepatitis B birth-dose vaccine (HepB-BD) for the prevention and control of hepatitis B (HepB). While prior studies suggest low coverage of...
Hepatitis B vaccine birth dose coverage among hepatitis B-exposed and hepatitis B-unexposed infants: evidence from the Healthy Beginning Initiative program in Benue State, Nigeria.
INTRODUCTION
Nigeria offers universal hepatitis B birth-dose vaccine (HepB-BD) for the prevention and control of hepatitis B (HepB). While prior studies suggest low coverage of HepB-BD in Nigeria, there is a paucity of evidence on the association between the uptake of HepB-BD and maternal HepB status. This study aimed to determine HepB-BD coverage and the associated factors among infants of HepB-positive and -negative women in Nigeria.
METHODS
the study was a secondary analysis of data from the Healthy Beginning Initiative program conducted between June 2016 and October 2018 in Benue State, Nigeria. The analysis was restricted to data from a cohort of 6269 mothers who had HepB screening during pregnancy and completed the HepB infant immunization question in the post-delivery survey. The association between the coverage of HepB-BD and maternal HepB status, sociodemographic characteristics, and obstetric factors were determined using crude and adjusted relative risks.
RESULTS
about 10% of the women tested HepB positive. The coverage of HepB-BD was 64% (63.2% among infants of HepB-positive mothers and 63.8% among HepB-negative mothers). The likelihood of infants of HepB-positive mothers receiving HepB-BD was not significantly different from infants of HepB-negative mothers (aRR=0.97, 95%CI= 0.92-1.04). Among HepB-positive mothers, infants of mothers younger than 20 years (aRR=1.49, 95%CI=1.03-2.16) or those who received antenatal care (aRR=1.41, 95%CI=1.16-1.71) were more likely to receive HepB-BD, while mothers with no previous pregnancies (aRR=0.73, 95%CI=0.59-0.91) were less likely to receive HepB-BD. Among HepB-negative mothers, infants of less-educated mothers were less likely to receive HepB-BD (aRR=0.96, 95%CI=0.92-0.99), whereas infants of mothers who received antenatal care (aRR=1.23, 95%CI=1.16-1.31) or had an institutional delivery were more likely (aRR=1.29, 95%CI=1.23-1.36) to receive HepB-BD. our findings highlight the need to improve HepB-BD uptake, particularly among HepB-exposed infants who are at risk of perinatal transmission of HepB.
Topics: Humans; Nigeria; Female; Hepatitis B; Pregnancy; Hepatitis B Vaccines; Adult; Young Adult; Vaccination Coverage; Infant, Newborn; Pregnancy Complications, Infectious; Infant; Infectious Disease Transmission, Vertical; Immunization Programs; Cohort Studies; Adolescent; Vaccination
PubMed: 38681098
DOI: 10.11604/pamj.2024.47.67.40466