The kinetics and durability of antibody and T-cell responses to SARS-CoV-2 in children.

BACKGROUND: The kinetics and durability of T-cell responses to SARS-CoV-2 in children are not well-characterized. We studied a cohort of children aged 6 months to 20 years with COVID-19 in whom peripheral blood mononuclear cells (PBMC) and sera were archived at approximately 1, 6, and 12 months post-symptom onset. METHODS: We compared antibody (N = 85) and T-cell responses (N = 26) to nucleocapsid (N) and spike (S) glycoprotein over time across four age strata: 6 months to 5 years, 5-9, 10-14, and 15-20 years. RESULTS: N-specific antibody responses declined over time, becoming undetectable in 26/32 (81%) children by approximately one year post-infection. Functional breadth of anti-N CD4+ T-cell responses also declined over time and were positively correlated with N-antibody responses (Pearson's r = 0.31, p = 0.008). CD4+ T-cell responses to S displayed greater functional breadth than N in unvaccinated children, and, along with neutralization titers, were stable over time and similar across age strata. Functional profiles of CD4+ T-cell responses against S were not significantly modulated by vaccination. CONCLUSIONS: Our data reveal durable, age-independent T-cell immunity to SARS-CoV-2 structural proteins in children over time following COVID-19 infection as well as S-Ab responses overall, in comparison to declining antibody responses to N.

T-SPOT.TB Reactivity in Southern African Children With and Without in Utero Human Immunodeficiency Virus Exposure.

Infants who are human immunodeficiency virus (HIV)-exposed uninfected (iHEU) experience higher risk of infectious morbidity than infants HIV-unexposed uninfected (iHUU). We compared tuberculosis (TB) infection prevalence in 418 Bacillus Calmette-Guérin vaccinated sub-Saharan African iHEU and iHUU aged 9-18 months using T-SPOT.TB. Prevalence of TB infection was low and did not differ by HIV exposure status.

Nanomaterials-based vaccines to target intracellular bacterial pathogens.

Development of novel immunization approaches to combat a growing list of emerging and ancient infectious agents is a global health priority. Intensive efforts over the last several decades have identified alternative approaches to improve upon traditional vaccines that are based on live, attenuated agents, or formulations of inactivated agents with adjuvants. Rapid advances in RNA-based and other delivery systems for immunization have recently revolutionized the potential to protect populations from viral pathogens, such as SARS-CoV-2. Similar efforts to combat bacterial pathogens, especially species with an intracellular niche, have lagged significantly. In the past decade, advances in nanotechnology have yielded a variety of new antigen/adjuvant carrier systems for use in vaccine development against infectious viruses and bacteria. The tunable properties of nanomaterial-based vaccines allow for balancing immunogenicity and safety which is a key hurdle in traditional antigen and adjuvant formulations. In this review, we discuss several novel nanoparticle-based vaccine platforms that show promise for use against intracellular bacteria as demonstrated by the feasibility of construction, enhanced antigen presentation, induction of cell mediated and humoral immune responses, and improved survival outcomes in in vivo models.

Self-adjuvanting nanovaccines boost lung-resident CD4+ T cell immune responses in BCG-primed mice.

Heterologous vaccine regimens could extend waning protection in the global population immunized with Mycobacterium bovis Bacille Calmette-Guerin (BCG). We demonstrate that pulmonary delivery of peptide nanofibers (PNFs) bearing an Ag85B CD4+ T cell epitope increased the frequency of antigen-specific T cells in BCG-primed mice, including heterogenous populations with tissue resident memory (Trm) and effector memory (Tem) phenotype, and functional cytokine recall. Adoptive transfer of dendritic cells pulsed with Ag85B-bearing PNFs further expanded the frequency and functional repertoire of memory CD4+ T cells. Transcriptomic analysis suggested that the adjuvanticity of peptide nanofibers is, in part, due to the release of damage-associated molecular patterns. A single boost with monovalent Ag85B PNF in BCG-primed mice did not reduce lung bacterial burden compared to BCG alone following aerosol Mtb challenge. These findings support the need for novel BCG booster strategies that activate pools of Trm cells with potentially diverse localization, trafficking, and immune function.

Baseline mapping of Oropouche virology, epidemiology, therapeutics, and vaccine research and development.

Oropouche virus (OROV) is an arthropod-borne orthobunyavirus found in South America and causes Oropouche fever, a febrile infection similar to dengue. It is the second most prevalent arthropod-borne viral disease in South America after dengue. Over 500,000 cases have been diagnosed since the virus was first discovered in 1955; however, this is likely a significant underestimate given the limited availability of diagnostics. No fatalities have been reported to date, however, up to 60% of cases have a recurrent phase of disease within one month of recovery from the primary disease course. The main arthropod vector is the biting midge Culicoides paraensis, which has a geographic range as far north as the United States and demonstrates the potential for OROV to geographically expand. The transmission cycle is incompletely understood and vertebrate hosts include both non-human primates and birds further supporting the potential ability of the virus to spread. A number of candidate antivirals have been evaluated against OROV in vitro but none showed antiviral activity. Surprisingly, there is only one report in the literature on candidate vaccines. We suggest that OROV is an undervalued pathogen much like chikungunya, Schmallenberg, and Zika viruses were before they emerged. Overall, OROV is an important emerging disease that has been under-investigated and has the potential to cause large epidemics in the future. Further research, in particular candidate vaccines, is needed for this important pathogen.

Peptide-based supramolecular vaccine systems.

Currently approved replication-competent and inactivated vaccines are limited by excessive reactogenicity and poor safety profiles, while subunit vaccines are often insufficiently immunogenic without co-administering exogenous adjuvants. Self-assembling peptide-, peptidomimetic-, and protein-based biomaterials offer a means to overcome these challenges through their inherent modularity, multivalency, and biocompatibility. As these scaffolds are biologically derived and present antigenic arrays reminiscent of natural viruses, they are prone to immune recognition and are uniquely capable of functioning as self-adjuvanting vaccine delivery vehicles that improve humoral and cellular responses. Beyond this intrinsic immunological advantage, the wide range of available amino acids allows for facile de novo design or straightforward modifications to existing sequences. This has permitted the development of vaccines and immunotherapies tailored to specific disease models, as well as generalizable platforms that have been successfully applied to prevent or treat numerous infectious and non-infectious diseases. In this review, we briefly introduce the immune system, discuss the structural determinants of coiled coils, ß-sheets, peptide amphiphiles, and protein subunit nanoparticles, and highlight the utility of these materials using notable examples of their innate and adaptive immunomodulatory capacity. STATEMENT OF SIGNIFICANCE: Subunit vaccines have recently gained considerable attention due to their favorable safety profiles relative to traditional whole-cell vaccines; however, their reduced efficacy requires co-administration of reactogenic adjuvants to boost immune responses. This has led to collaborative efforts between engineers and immunologists to develop nanomaterial-based vaccination platforms that can elicit protection without deleterious side effects. Self-assembling peptidic biomaterials are a particularly attractive approach to this problem, as their structure and function can be controlled through primary sequence design and their capacity for multivalent presentation of antigens grants them intrinsic self-adjuvanticity. This review introduces the various architectures adopted by self-assembling peptides and discusses their application as modulators of innate and adaptive immunity.