• Atypical B cells are part of an alternative lineage of B cells that participates in responses to vaccination and infection in humans

      Sutton, H.J.; Aye, R.; Idris, A.H.; Vistein, R.; Nduati, E.; Kai, O.; Mwacharo, J.; Li, X.; Gao, X.; Andrews, T.D.; et al. (Elsevier B.V., 2021-02-09)
      The diversity of circulating human B cells is unknown. We use single-cell RNA sequencing (RNA-seq) to examine the diversity of both antigen-specific and total B cells in healthy subjects and malaria-exposed individuals. This reveals two B cell lineages: a classical lineage of activated and resting memory B cells and an alternative lineage, which includes previously described atypical B cells. Although atypical B cells have previously been associated with disease states, the alternative lineage is common in healthy controls, as well as malaria-exposed individuals. We further track Plasmodium-specific B cells after malaria vaccination in naive volunteers. We find that alternative lineage cells are primed after the initial immunization and respond to booster doses. However, alternative lineage cells develop an atypical phenotype with repeated boosts. The data highlight that atypical cells are part of a wider alternative lineage of B cells that are a normal component of healthy immune responses. Copyright 2021 The Author(s)Using single-cell RNA sequencing, Sutton et al. show that a population of "atypical" B cells, normally associated with disease, are part of a wider landscape of alternative B cells that participate in normal responses to vaccination. Copyright 2021 The Author(s)
    • Burden of measles in Nigeria: a five-year review of casebased surveillance data, 2012-2016

      Ibrahim, B.S.; Usman, R.; Mohammed, Y. (NLM (Medline), 2019)
      Introduction: measles is a vaccine preventable, highly transmissible viral infection that affects mostly children under five years. We reviewed surveillance data on measles from Nigeria over a five-year period to highlights its burden and make recommendations for improvements. Methods: we conducted a secondary data analysis of measles specific Integrated Disease Surveillance and Response (IDSR) records of all states in Nigeria over a five-year period. Results: a total of 131,732 cases were recorded between January 2012 and September 2016. Most cases 57,892 (43.95%) were recorded in 2013 while the least 11,061 (8.4%) were recorded in 2012. A total of 817 deaths were recorded, with a case fatality rate (CFR) of 0.62%. The highest CFR (1.43%) was recorded in 2012 while the least CFR (0.44%) was recorded in 2016. Only 8,916 (6.7%) cases were confirmed by laboratory tests. The trend of measles cases followed the same pattern throughout the years under review, with cases peaking at March, then gradually reducing to lowest level at June, which was maintained throughout the rest of the year. States in northern region of Nigeria recorded the highest attack rate (Yobe: 480.29 cases per 100,000 population, Sokoto: 284.63 cases per 100,000 population and Katsina: 246.07 cases per 100,000 population) compared to States in the southern region (Rivers: 11.72 cases per 100,000 population and Akwa Ibom: 13.59 cases per 100,000 population). Conversely, States in the southern region recorded the highest CFR (Ebonyi: 13.43% and Rivers: 3.27%). Conclusion: measles infection remains a burden especially in the northern region of Nigeria. Although measles fatalities declined over the years, laboratory confirmation was sub-optimal. We recommended improvement on routine immunization and strengthening of regional laboratories diagnostic capacities, for successful eradication of measles from Nigeria.
    • Forecasting Demand for the Typhoid Conjugate Vaccine in Low- and Middle-income Countries

      Debellut, F.; Hendrix, N.; Pitzer, V.E. (Oxford University Press, 2019)
      BACKGROUND: The World Health Organization (WHO) released a position paper in March 2018 calling for integration of a novel typhoid conjugate vaccine (TCV) into routine immunization along with catch-up campaigns for children up to age 15. Gavi, the Vaccine Alliance, has committed funding to help resource-constrained countries introduce this vaccine. In this article, the Typhoid Vaccine Acceleration Consortium forecasts demand if WHO recommendations are followed. METHODS: We built a model of global TCV introductions between 2020 and 2040 to estimate the demand of the vaccine for 133 countries. We estimated each country's year of introduction by examining its estimated incidence of typhoid fever, its history of introducing new vaccines, and any knowledge we have of its engagement with typhoid prevention, including intention to apply for Gavi funding. Our model predicted use in routine infant vaccination as well as campaigns targeting varying proportions of the unvaccinated population up to 15 years of age. RESULTS: Between 2020 and 2025, demand will predominantly come from African countries, many receiving Gavi support. After that, Asian countries generate most demand until 2030, when campaigns are estimated to end. Demand will then track the birth cohort of participating countries, suggesting an annual routine demand between 90 and 100 million doses. Peak demand is likely to occur between 2023 and 2026, approaching 300 million annual doses if campaign implementation is high. CONCLUSIONS: In our analysis, target population for catch-up campaigns is the main driver of uncertainty. At peak demand, there is some risk of exceeding presently estimated peak production capacity. Therefore, it will be important to carefully coordinate introductions, especially when accompanied by campaigns targeting large proportions of the eligible population. © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
    • Role of immunotherapy in Ewing sarcoma

      Morales, E.; Olson, M.; Iglesias, F.; Dahiya, S.; Luetkens, T.; Atanackovic, D. (BMJ Publishing Group, 2020)
      Ewing sarcoma (ES) is thought to arise from mesenchymal stem cells and is the second most common bone sarcoma in pediatric patients and young adults. Given the dismal overall outcomes and very intensive therapies used, there is an urgent need to explore and develop alternative treatment modalities including immunotherapies. In this article, we provide an overview of ES biology, features of ES tumor microenvironment (TME) and review various tumor-Associated antigens that can be targeted with immune-based approaches including cancer vaccines, monoclonal antibodies, T cell receptor-Transduced T cells, and chimeric antigen receptor T cells. We highlight key reasons for the limited efficacy of various immunotherapeutic approaches for the treatment of ES to date. These factors include absence of human leukocyte antigen class I molecules from the tumor tissue, lack of an ideal surface antigen, and immunosuppressive TME due to the presence of myeloid-derived suppressor cells, F2 fibrocytes, and M2-like macrophages. Lastly, we offer insights into strategies for novel therapeutics development in ES. These strategies include the development of gene-modified T cell receptor T cells against cancer-Testis antigen such as XAGE-1, surface target discovery through detailed profiling of ES surface proteome, and combinatorial approaches. In summary, we provide state-of-The-Art science in ES tumor immunology and immunotherapy, with rationale and recommendations for future therapeutics development.
    • Vaccine-related major cutaneous reaction size correlates with cellular-mediated immune responses after tularaemia immunisation

      Salerno-Gonçalves, Rosangela; Chen, Wilbur H; Mulligan, Mark J; Frey, Sharon E; Stapleton, Jack T; Keitel, Wendy A; Bailey, Jason; Sendra, Eli; Hill, Heather; Johnson, Robert A; et al. (John Wiley and Sons Inc., 2021-01-19)
      Francisella tularensis, the causative agent of tularaemia, is an exceptionally infectious bacterium, potentially fatal for humans if left untreated and with the potential to be developed as a bioweapon. Both natural infection and live-attenuated vaccine strain (LVS) confer good protection against tularaemia. LVS vaccination is traditionally administered by scarification, and the formation of a cutaneous reaction or take at the vaccination site is recognised as a clinical correlate of protection. Although previous studies have suggested that high antibody titres following vaccination might serve as a useful surrogate marker, the immunological correlates of protection remain unknown.
    • Warp Speed for Coronavirus Disease 2019 (COVID-19) Vaccines: Why Are Children Stuck in Neutral?

      Anderson, Evan J; Campbell, James D; Creech, C Buddy; Frenck, Robert; Kamidani, Satoshi; Munoz, Flor M; Nachman, Sharon; Spearman, Paul (Oxford University Press, 2020-09-18)
      While adult clinical trials of coronavirus disease 2019 (COVID-19) vaccines have moved quickly into phase 3 clinical trials, clinical trials have not started in children in the United States. The direct COVID-19 impact upon children is greater than that observed for a number of other pathogens for which we now have effective pediatric vaccines. Additionally, the role of children in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has clearly been underappreciated. Carefully conducted phase 2 clinical trials can adequately address potential COVID-19 vaccine safety concerns. Delaying phase 2 vaccine clinical trials in children will delay our recovery from COVID-19 and unnecessarily prolong its impact upon children's education, health, and emotional well-being, and equitable access to opportunities for development and social success. Given the potential direct and indirect benefits of pediatric vaccination, implementation of phase 2 clinical trials for COVID-19 vaccines should begin now.