Durable Vaccine Research Articles

Nanomaterials in Immunology: Bridging Innovative Approaches in Immune Modulation, Diagnostics, and Therapy.

The intersection of immunology and nanotechnology has provided significant advancements in biomedical research and clinical applications over the years. Immunology aims to understand the immune system's defense mechanisms against pathogens. Nanotechnology has demonstrated its potential to manipulate immune responses, as nanomaterials' properties can be modified for the desired application. Research has shown that nanomaterials can be applied in diagnostics, therapy, and vaccine development. In diagnostics, nanomaterials can be used for biosensor development, accurately detecting biomarkers even at very low concentrations. Therapeutically, nanomaterials can act as efficient carriers for delivering drugs, antigens, or genetic material directly to targeted cells or tissues. This targeted delivery improves therapeutic efficacy and reduces the adverse effects on healthy cells and tissues. In vaccine development, nanoparticles can improve vaccine durability and extend immune responses by effectively delivering adjuvants and antigens to immune cells. Despite these advancements, challenges regarding the safety, biocompatibility, and scalability of nanomaterials for clinical applications are still present. This review will cover the fundamental interactions between nanomaterials and the immune system, their potential applications in immunology, and their safety and biocompatibility concerns.

Make it a combo.

Adjuvants that combine TLR agonists and inflammatory agonists promote robust and durable vaccine responses (Bechtold et al. and Arunachalam et al.).

RAAV expressing a COBRA-designed influenza hemagglutinin generates a protective and durable adaptive immune response with a single dose.

Developing an improved seasonal influenza vaccine remains an ambitious goal of researchers and clinicians alike. With influenza routinely causing severe epidemics with the potential to rise to pandemic levels, it is critical to create an effective, broadly protective, and durable vaccine to improve public health worldwide. As a potential solution, we created a rAAV viral vector expressing a COBRA-optimized influenza hemagglutinin antigen with modestly enriched CpG motifs to evoke a robust and long-lasting immune response after a single intramuscular dose without needing boosts or adjuvants. Importantly, the rAAV vaccine boosted antibody breadth to future strains in ferrets with pre-existing influenza immunity. Together, our data support further investigation into the utility of viral vectors as a potential avenue to improve our seasonal influenza vaccines.

Burden of Vaccine-Preventable Diseases in People Living with HIV.

Vaccine-preventable diseases (VPDs) pose a serious public health concern for people living with HIV (PLH). PLH experience a delayed and weakened response to many vaccines available, compared to the general population. Lower seroconversion rates, along with a decreased efficacy and durability of vaccines, increases the susceptibility of PLH to VPDs. Vaccination guidelines specifically targeting this population have been modified to overcome these challenges. However, vaccine uptake remains suboptimal due to multiple barriers, highlighting the need for further studies and the additional implementation of public health measures specifically tailored to PLH.

Modulating Adjuvant Release Kinetics From Scaffold Vaccines to Tune Adaptive Immune Responses.

Increasing the potency, quality, and durability of vaccines represents a major public health challenge. A critical parameter that shapes vaccine immunity is the spatiotemporal context in which immune cells interact with antigen and adjuvant. While various material-based strategies demonstrate that extended antigen release enhances both cellular and humoral immunity, the effect of adjuvant kinetics on vaccine-mediated immunity remains incompletely understood. Here, a previously characterized mesoporous silica rod (MPS) biomaterial vaccine is used to develop a facile, electrostatics-driven approach to tune in vivo kinetics of the TLR9 agonist cytosine phosphoguanosine oligodeoxynucleotide (CpG). It is demonstrated that rapid release of CpG from MPS vaccines, mediated by alterations in MPS chemistry that tune surface charge, generates potent cytotoxic T cell responses and robust, T helper type 1 (Th1)-skewed IgG2a/c antibody titers. Immunophenotyping of lymphoid organs after MPS vaccination with slow or fast CpG release kinetics suggests that differential engagement of migratory dendritic cells and natural killer cells may contribute to the more potent responses observed with rapid adjuvant release. Taken together, these findings suggest that vaccine approaches that pair sustained release of antigen with rapid release of adjuvants with similar characteristics to CpG may drive particularly potent Th1 responses.

Designing of multi-Epitope vaccine against spike glycoprotein of SARS-CoV-2 using immunoinformatics approach

BackgroundCOVID-19 caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome) has created an alarming situation worldwide. The surface (S) glycoprotein of novel coronavirus, encoded by the genome of SARS-CoV-2, plays an role in attachment, fusion as well as entry into the host cell. The spike glycoprotein plays vital role in not only infection but pathogenesis and adaptive immunity, and, therefore, the S glycoprotein is considered as the main target for the development of effective and durable vaccine against SARS-CoV-2. Present study aims to compare the SARS-CoV-2 spike sequence obtained from first Wuhan virus with those of Asian SARS-CoV-2 isolates. ResultA total of 1165 mutations from 657 sequences of Asia submitted in the month of November 2020 to February 2021 were detected. Further, secondary structure prediction followed by protein modeling analysis was performed which revealed, these mutations, considerably altered the stability of Spike protein. Additionally, Physiochemical properties, toxicity, allergenicity and stability of spike glycoprotein were estimated to demonstrate the specificity of the epitope candidates. Subsequently, we identified a total of 34B-cell and 10 T-cell immune epitopes. Among the predicted epitopes, 26 B-cell and 9T-cell epitopes showed non-allergenic, non-toxic and highly antigenic properties. ConclusionTaken together, our study showed spike glycoprotein of SARS-CoV-2 can be a potentially good candidate for the development of vaccine to curb SARS-CoV-2 infections.

Clinically relevant atovaquone-resistant human malaria parasites fail to transmit by mosquito

Long-acting injectable medications, such as atovaquone, offer the prospect of a “chemical vaccine” for malaria, combining drug efficacy with vaccine durability. However, selection and transmission of drug-resistant parasites is of concern. Laboratory studies have indicated that atovaquone resistance disadvantages parasites in mosquitoes, but lack of data on clinically relevant Plasmodium falciparum has hampered integration of these variable findings into drug development decisions. Here we generate atovaquone-resistant parasites that differ from wild type parent by only a Y268S mutation in cytochrome b, a modification associated with atovaquone treatment failure in humans. Relative to wild type, Y268S parasites evidence multiple defects, most marked in their development in mosquitoes, whether from Southeast Asia (Anopheles stephensi) or Africa (An. gambiae). Growth of asexual Y268S P. falciparum in human red cells is impaired, but parasite loss in the mosquito is progressive, from reduced gametocyte exflagellation, to smaller number and size of oocysts, and finally to absence of sporozoites. The Y268S mutant fails to transmit from mosquitoes to mice engrafted with human liver cells and erythrocytes. The severe-to-lethal fitness cost of clinically relevant atovaquone resistance to P. falciparum in the mosquito substantially lessens the likelihood of its transmission in the field.

The Global Mpox Outbreak andEffective Vaccine Communication.

The effectiveness and durability of vaccination to protect against localized anogenital mpox skin lesions is not well defined. Overestimating vaccine effectiveness against mild infection risks degrading vaccine confidence. Acknowledging and communicating vaccine unknowns and limitations is vital to direct mpox research, maintain vaccine confidence, and optimize uptake.

Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID-19–Associated Hospitalization and Critical Illness Among Adults with and Without Immunocompromising Conditions — VISION Network, September 2022–April 2023

Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID-19–Associated Hospitalization and Critical Illness Among Adults with and Without Immunocompromising Conditions — VISION Network, September 2022–April 2023

Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID-19–Associated Hospitalization and Critical Illness Among Adults with and Without Immunocompromising Conditions — VISION Network, September 2022–April 2023

On September 1, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended a single bivalent mRNA COVID-19 booster dose for persons aged ≥12 years who had completed at least a monovalent primary series. Early vaccine effectiveness (VE) estimates among adults aged ≥18 years showed receipt of a bivalent booster dose provided additional protection against COVID-19-associated emergency department and urgent care visits and hospitalizations compared with that in persons who had received only monovalent vaccine doses (1); however, insufficient time had elapsed since bivalent vaccine authorization to assess the durability of this protection. The VISION Network* assessed VE against COVID-19-associated hospitalizations by time since bivalent vaccine receipt during September 13, 2022-April 21, 2023, among adults aged ≥18 years with and without immunocompromising conditions. During the first 7-59 days after vaccination, compared with no vaccination, VE for receipt of a bivalent vaccine dose among adults aged ≥18 years was 62% (95% CI=57%-67%) among adults without immunocompromising conditions and 28% (95% CI=10%-42%) among adults with immunocompromising conditions. Among adults without immunocompromising conditions, VE declined to 24% (95% CI=12%-33%) among those aged ≥18 years by 120-179 days after vaccination. VE was generally lower for adults with immunocompromising conditions. A bivalent booster dose provided the highest protection, and protection was sustained through at least 179 days against critical outcomes, including intensive care unit (ICU) admission or in-hospital death. These data support updated recommendations allowing additional optional bivalent COVID-19 vaccine doses for certain high-risk populations. All eligible persons should stay up to date with recommended COVID-19 vaccines.

The impact of primary immunization route on the outcome of infection with SARS-CoV-2 in a hamster model of COVID-19.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in over 6.7 million deaths worldwide. COVID-19 vaccines administered parenterally via intramuscular or subcutaneous (SC) routes have reduced the severity of respiratory infections, hospitalization rates, and overall mortality. However, there is a growing interest in developing mucosally delivered vaccines to further enhance the ease and durability of vaccination. This study compared the immune response in hamsters immunized with live SARS-CoV-2 virus via SC or intranasal (IN) routes and assessed the outcome of a subsequent IN SARS-CoV-2 challenge. Results showed that SC-immunized hamsters elicited a dose-dependent neutralizing antibody response but of a significantly lower magnitude than that observed in IN-immunized hamsters. The IN challenge with SARS-CoV-2 in SC-immunized hamsters resulted in body weight loss, increased viral load, and lung pathology than that observed in IN-immunized and IN-challenged counterparts. These results demonstrate that while SC immunization renders some degree of protection, IN immunization induces a stronger immune response and better protection against respiratory SARS-CoV-2 infection. Overall, this study provides evidence that the route of primary immunization plays a critical role in determining the severity of a subsequent respiratory infection caused by SARS-CoV-2. Furthermore, the findings suggest that IN route of immunization may be a more effective option for COVID-19 vaccines than the currently used parenteral routes. Understanding the immune response to SARS-CoV-2 elicited via different immunization routes may help guide more effective and long-lasting vaccination strategies.

An old dog with ‘new’ tricks: the MDR1 transporter in T cell-mediated immunity

Abstract Multidrug Resistance Protein 1 (MDR1) is an orphan ATP-binding cassette transporter, originally discovered for removing cytostatic drugs from resistant tumor cells. However, MDR1 is also functionally expressed in many normal cell types. Work from our group has shown that MDR1 is constitutively expressed in cytotoxic T cells (CTLs), where it promotes CTL-mediated immunity to infection. Adoptive transfer of Lymphocytic choriomeningitis virus (LCMV)-specific MDR1 (Abcb1a/b)-deficient naïve CTLs into wild-type recipients, followed by LCMV infection, has revealed that MDR1-deficient CTLs fail to accumulate to wild-type levels in response to either acute (Armstrong) or chronic (Clone-13) LCMV infection. This defective accumulation is observed as early as 5-days post-infection, suggesting that endogenous MDR1 transport activity may preferentially regulate early T cell receptor (TCR)-elicited CTL functions. New single cell (sc)RNA-seq experiments, coupled with RNA velocity and lineage trajectory analyses, suggest that MDR1 expression is induced rapidly during TCR activation, coinciding with the induction of other genes involved in mitochondrial and redox metabolism. In vitro-activated CTLs lacking MDR1 also experience oxidative stress, mitochondrial dysfunction and display mitochondrial localization of MDR1. Together, these data support a new model of MDR1 function, in which MDR1-dependent transport of endogenous substrates suppresses oxidative stress and supports redox homeostasis during periods of metabolic activation. In turn, these concepts provide a novel framework for improving the efficacy and durability of vaccines, and for elucidating metabolic vulnerabilities of multidrug-resistant cancers.

Glycosylated nanoparticle-based PfCSP vaccine confers long-lasting antibody responses and sterile protection in mouse malaria model

The development of an effective and durable vaccine remains a central goal in the fight against malaria. Circumsporozoite protein (CSP) is the major surface protein of sporozoites and the target of the only licensed Plasmodium falciparum (Pf) malaria vaccine, RTS,S/AS01. However, vaccine efficacy is low and short-lived, highlighting the need for a second-generation vaccine with superior efficacy and durability. Here, we report a Helicobacter pylori apoferritin-based nanoparticle immunogen that elicits strong B cell responses against PfCSP epitopes that are targeted by the most potent human monoclonal antibodies. Glycan engineering of the scaffold and fusion of an exogenous T cell epitope enhanced the anti-PfCSP B cell response eliciting strong, long-lived and protective humoral immunity in mice. Our study highlights the power of rational vaccine design to generate a highly efficacious second-generation anti-infective malaria vaccine candidate and provides the basis for its further development.

Induction of antigen specific intrahepatic CD8+ T cell responses by a secreted heat shock protein based gp96-Ig-PfCA malaria vaccine.

A highly efficacious and durable vaccine against malaria is an essential tool for global malaria eradication. One of the promising strategies to develop such a vaccine is to induce robust CD8+ T cell mediated immunity against malaria liver-stage parasites. Here we describe a novel malaria vaccine platform based on a secreted form of the heat shock protein, gp96-immunoglobulin, (gp96-Ig) to induce malaria antigen specific, memory CD8+ T cells. Gp96-Ig acts as an adjuvant to activate antigen presenting cells (APCs) and chaperone peptides/antigens to APCs for cross presentation to CD8+ T cells. Our study shows that vaccination of mice and rhesus monkeys with HEK-293 cells transfected with gp96-Ig and two well-known Plasmodium falciparum CSP and AMA1 (PfCA) vaccine candidate antigens, induces liver-infiltrating, antigen specific, memory CD8+ T cell responses. The majority of the intrahepatic CSP and AMA1 specific CD8+ T cells expressed CD69 and CXCR3, the hallmark of tissue resident memory T cells (Trm). Also, we found intrahepatic, antigen-specific memory CD8+ T cells secreting IL-2, which is relevant for maintenance of effective memory responses in the liver. Our novel gp96-Ig malaria vaccine strategy represents a unique approach to induce liver-homing, antigen-specific CD8+ T cells critical for Plasmodium liver-stage protection.

A transcriptionally distinct subset of influenza-specific effector memory B cells predicts long-lived antibody responses to vaccination in humans

Seasonal influenza vaccination elicits hemagglutinin (HA)-specific memory B (Bmem) cells, and although multiple Bmem cell populations have been characterized, considerable heterogeneity exists. We found that HA-specific human Bmem cells differed in the expression of surface marker FcRL5 and transcriptional factor T-bet. FcRL5+T-bet+ Bmem cells were transcriptionally similar to effector-like memory cells, while T-betnegFcRL5neg Bmem cells exhibited stem-like central memory properties. FcRL5+ Bmem cells did not express plasma-cell-commitment factors but did express transcriptional, epigenetic, metabolic, and functional programs that poised these cells for antibody production. Accordingly, HA+ T-bet+ Bmem cells at day 7 post-vaccination expressed intracellular immunoglobulin, and tonsil-derived FcRL5+ Bmem cells differentiated more rapidly into antibody-secreting cells (ASCs) invitro. The T-bet+ Bmem cell response positively correlated with long-lived humoral immunity, and clonotypes from T-bet+ Bmem cells were represented in the secondary ASC response to repeat vaccination, suggesting that this effector-like population predicts influenza vaccine durability and recall potential.

Seasonal trends in COVID-19 cases, hospitalizations, and mortality in the United States and Europe

Determining whether SARS-CoV-2 exhibits seasonality like other respiratory viruses is critical for public health planning. We evaluated whether COVID-19 rates follow a seasonal pattern using time series models. We used time series decomposition to extract the annual seasonal component of COVID-19 case, hospitalization, and mortality rates from March 2020 through December 2022 for the United States and Europe. Models were adjusted for a country-specific stringency index to account for confounding by various interventions. Despite year-round disease activity, we identified seasonal spikes in COVID-19 from approximately November through April for all outcomes and in all countries. Our results support employing annual preventative measures against SARS-CoV-2, such as administering seasonal booster vaccines in a similar timeframe as those in place for influenza. Whether certain high-risk individuals may need more than one COVID-19 vaccine booster dose each year will depend on factors like vaccine durability against severe illness and levels of year-round disease activity.

Robust induction of functional humoral response by a plant-derived Coronavirus-like particle vaccine candidate for COVID-19

Despite the success of existing COVID-19 vaccine platforms, the persistent limitations in global deployment of vaccines and waning immunity exhibited by many of the currently deployed vaccine platforms have led to perpetual outbreaks of SARS-CoV-2 variants of concern. Thus, there is an urgent need to develop new durable vaccine candidates, to expand the global vaccine pipeline, and provide safe and effective solutions for every country worldwide. Here we deeply profiled the functional humoral response induced by two doses of AS03-adjuvanted and non-adjuvanted plant-derived Coronavirus-like particle (CoVLP) vaccine candidate from the phase 1 clinical trial, at peak immunogenicity and six months post-vaccination. AS03-adjuvanted CoVLP induced robust and durable SARS-CoV-2 specific humoral immunity, marked by strong IgG1antibody responses, potent FcγR binding, and antibody effector function. Contrary to a decline in neutralizing antibody titers, the FcγR2A-receptor binding capacity and antibody-mediated effector functions, such as opsonophagocytosis, remained readily detectable for at least six months.

P733 Novelties of COVID-19 vaccination beyond efficacy: Nationwide experiences with trough levels, durability, and disease activity among inflammatory bowel disease patients

Abstract Background The SARS-CoV-2 pandemic has raised issues in the management of inflammatory bowel diseases (IBD). This study aimed to assess the efficacy of different anti-SARS-CoV-2 vaccines under different treatments in IBD patients and identify predictive factors associated with lower serological response, including anti-TNF drug levels. Methods A prospective, multicentre study of IBD patients was conducted following mRNA and non-mRNA anti-SARS-CoV-2 vaccination. Healthy control (HC) patients were enrolled to reduce bias. Baseline and week 14 samples were obtained following the second dose to assess the impact of conventional and biological treatments. Clinical and biochemical activity, serological response level, and anti-TNF drug levels were measured. Results This study included 199 IBD (Table 1.; mean age, 40.9 ± 12.72 years) and 77 HC participants. Most patients (76.9%) and all HCs received mRNA vaccines. Half of the IBD patients were on biological treatment (Table 2.; anti-TNF 68.7%). Combined immunomodulation and biological treatment were associated with lower serological response (Figure 1.; p<0.001), and mRNA vaccination promoted better antibody levels (p<0.001). Higher adalimumab levels caused lower serological response (p=0.006). W8 persistence of anti-SARS-CoV-2 level was equal in IBD and HC groups (Figure 2.; p>0.05). Vaccination had no impact on disease activity. Conclusion Anti-SARS-CoV-2 vaccination is considerably efficacious in IBD patients, with mRNA vaccines promoting better antibody levels. The negative impact of combined biological treatment, especially with high adalimumab drug levels, on serological response to vaccination should be considered. Although mid-term durability of vaccination is encouraging, more data are needed to expand existing understanding on this issue.

Nationwide experiences with trough levels, durability, and disease activity among inflammatory bowel disease patients following COVID-19 vaccination.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has complicated the management of inflammatory bowel diseases (IBD). This study aimed to assess the efficacy of different anti-SARS-CoV-2 vaccines under different treatments in IBD patients and identify predictive factors associated with lower serological response, including anti-tumor necrosis factor (anti-TNF) drug levels. A prospective, double-center study of IBD patients was conducted following messenger ribonucleotide acid (mRNA) and non-mRNA anti-SARS-CoV-2 vaccination. Healthy control (HC) patients were enrolled to reduce bias. Baseline and control samples were obtained 14 days after the second dose to assess the impact of conventional and biological treatments. Clinical and biochemical activity, serological response level, and anti-TNF drug levels were measured. This study included 199 IBD (mean age, 40.9 ± 12.72 years) and 77 HC participants (mean age, 50.3 ± 12.36 years). Most patients (76.9%) and all HCs received mRNA vaccines. Half of the IBD patients were on biological treatment (anti-TNF 68.7%). Biological and thiopurine combined immunomodulation and biological treatment were associated with lower serological response (p < 0.001), and mRNA vaccination promoted better antibody levels (p < 0.001). Higher adalimumab levels caused lower serological response (p = 0.006). W8 persistence of anti-SARS-CoV-2 level was equal in IBD and HC groups. Vaccination did not aggravate clinical disease activity (p = 0.65). Anti-SARS-CoV-2 vaccination is considerably efficacious in IBD patients, with mRNA vaccines promoting better antibody levels. The negative impact of combined biological treatment, especially with high adalimumab drug levels, on serological response to vaccination should be considered. Although midterm durability of vaccination is encouraging, more data are needed to expand the existing understanding on this issue.

Long-Term Vaccine Durability of Covid-19 Vaccines

Long-Term Vaccine Durability of Covid-19 Vaccines