Future Vaccine Research Articles

Cohort profile: an observational population-based cohort study on COVID-19 vaccine effectiveness in the Netherlands – the VAccine Study COVID-19 (VASCO)

PurposeVAccine Study COVID-19 (VASCO) is a cohort study with a 5-year follow-up that was initiated when COVID-19 vaccination was introduced in the Netherlands. The primary objective is to estimate real-world...

Hyperfunctional T cell responses unchecked by regulatory T cells are unable to resolve hepaciviral infection without humoral contribution

Background & AimsThe most recent T cell-based vaccine against hepatitis C virus (HCV) in human subjects failed to swing the pendulum from chronicity to resolution despite eliciting cellular responses in the majority of individuals. These results naturally evoke the question of whether hyperactivated responses of a single adaptive immune arm are capable of inducing HCV clearance or if coordinated efforts between antibodies and T cells are indeed necessary. Here, we sought to address this point in determining whether the suppression of antiviral T cell and IgG responses by regulatory T cells (Tregs) is a critical prerequisite of delayed viral clearance or overt chronicity. MethodsUsing a surrogate model of HCV infection, rodent hepacivirus (RHV) infection in mice, we utilized Foxp3-DTR mice to assess how Tregs modulate the generation of acute antiviral adaptive immune responses and indirectly dictate infection fate via intracellular flow cytometry staining, ELISA, RNA sequencing, and qPCR. ResultsTransient depletion of Tregs prior to infection decreased viral-specific CD4+ T cell function, IgG production, and delayed viral clearance. In contrast, transient Treg depletion after infection increased both T cell functionality and IgG production, thereby facilitating accelerated viral clearance. Hyperactivated T cells, achieved via transient Treg depletion, were unable to clear the virus as an isolated effector arm without the help of viral-specific IgG production. ConclusionsTregs control the outcome of RHV infection via direct modulation of CD4+ T cells and IgG production. Hyperactivated T cell responses are incapable of compensating for experimentally induced lack of antibodies, further reinforcing the notion of cooperative interplay between adaptive immune arms in facilitating hepaciviral clearance. Impact and implicationsWe demonstrate herein how timing of Treg depletion determines the fate of effector T cells, humoral responses, and the kinetics of viral clearance. Our observations provide direct evidence that functional T cell responses are incapable of compensating for suboptimal humoral responses in facilitating viral resolution. Our results imply that future HCV vaccine regimens should not solely rely on eliciting focused responses of a single effector arm, but rather incorporate immunogens capable of inducing durable features of both humoral and cellular memory.

Evidence brief on facilitators, barriers and hesitancy of COVID-19 booster doses in Canada.

Understanding the facilitators, barriers and hesitancy to accepting COVID-19 booster doses is important for encouraging recommended vaccination. This evidence brief summarizes literature on the intention to accept or reject COVID-19 vaccine booster doses and the factors associated with intention/uptake among individuals in Canada. A database of COVID-19 literature established at the Public Health Agency of Canada was searched for articles referencing vaccination and knowledge, attitudes and behaviours towards COVID-19 boosters. A grey literature search of Canadian governmental and academic institutions was also conducted. Primary research conducted in Canada (n=21) and relevant systematic reviews of the global literature (n=8) were included in this evidence brief. Intentions to get a booster dose in the general population have decreased between 2021-2023, with intentions varying across subpopulations. In Canada and within the global systematic reviews, facilitators, barriers and hesitancy were similar. Older age was the most common factor positively associated with intention/uptake of a booster, and the most common motivators were government/healthcare provider recommendations and helping to protect others. The main reasons for hesitancy were concerns about vaccine side effects and a lack of belief in the vaccine's efficacy. Intentions to get a booster dose have decreased in Canada. Understanding the reasons for vaccine hesitancy and motivators for obtaining a booster can help guide future public health COVID-19 booster vaccination programs.

COVID-19 Vaccine Hesitancy and Uptake Among Vaccinated Population in Malaysia

This study identified the significant COVID-19 vaccine hesitancy and intention to uptake motives and sociodemographic predictors among vaccinated Malaysian adults. A cross-sectional study using a self-administered online questionnaire adapted from the COVID-19 Vaccine Hesitancy Scale and extended based on previous studies was used to solicit data from 698 Malaysians. A theoretical framework comprising Trust, Vaccine Concerns, Unreliable Entities, Uptake Influencers, Brand Influencers, and Brand_Side-effect was used as a guide to assess intention to receive COVID-19 vaccines in the future. Hierarchical linear regressions revealed Trust, Vaccine Concerns, Brand_Side-effect and Uptake Influencers to significantly predict intention to receive vaccines in the future when controlled for sociodemographic correlates. Ethnicity and technology literacy were found to have significant impacts on future vaccine uptake. Age significantly correlated with intention to be vaccinated as well. Underlying motives and sociodemographic correlates were identified for COVID-19 vaccine hesitancy and uptake.

Predicting COVID-19 booster immunogenicity against future SARS-CoV-2 variants and the benefits of vaccine updates

The ongoing evolution of the SARS-CoV-2 virus has led to a move to update vaccine antigens in 2022 and 2023. These updated antigens were chosen and approved based largely on in vitro neutralisation titres against recent SARS-CoV-2 variants. However, unavoidable delays in vaccine manufacture and distribution meant that the updated booster vaccine was no longer well-matched to the circulating SARS-CoV-2 variant by the time of its deployment. Understanding whether the updating of booster vaccine antigens improves immune responses to subsequent SARS-CoV-2 circulating variants is a major priority in justifying future vaccine updates. Here we analyse all available data on the immunogenicity of variants containing SARS-CoV-2 vaccines and their ability to neutralise later circulating SARS-CoV-2 variants. We find that updated booster antigens give a 1.4-fold [95% CI: 1.07–1.82] greater increase in neutralising antibody levels when compared with a historical vaccine immunogen. We then use this to predict the relative protection that can be expected from an updated vaccine even when the circulating variant has evolved away from the updated vaccine immunogen. These findings help inform the rollout of future booster vaccination programmes.

Impact of pneumococcal conjugate vaccines on invasive pneumococcal disease-causing lineages among South African children

Invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCV) remains a global concern. This study used pathogen genomics to evaluate changes in invasive pneumococcal lineages before, during and after vaccine introduction in South Africa. We included genomes (N = 3104) of IPD isolates from individuals aged <18 years (2005–20), spanning four periods: pre-PCV, PCV7, early-PCV13, and late-PCV13. Significant incidence reductions occurred among vaccine-type lineages in the late-PCV13 period compared to the pre-PCV period. However, some vaccine-type lineages continued to cause invasive disease and showed increasing effective population size trends in the post-PCV era. A significant increase in lineage diversity was observed from the PCV7 period to the early-PCV13 period (Simpson’s diversity index: 0.954, 95% confidence interval 0.948-0.961 vs 0.965, 0.962-0.969) supporting intervention-driven population structure perturbation. Increases in the prevalence of penicillin, erythromycin, and multidrug resistance were observed among non-vaccine serotypes in the late-PCV13 period compared to the pre-PCV period. In this work we highlight the importance of continued genomic surveillance to monitor disease-causing lineages post vaccination to support policy-making and future vaccine designs and considerations.

Urban wastewater contains a functional human antibody repertoire of mucosal origin

Wastewater-based surveillance of human disease offers timely insights to public health, helping to mitigate infectious disease outbreaks and decrease downstream morbidity and mortality. These systems rely on nucleic acid amplification tests for monitoring disease trends, while antibody-based seroprevalence surveys gauge community immunity. However, serological surveys are resource-intensive and subject to potentially long lead times and sampling bias. We identified and characterized a human antibody repertoire, predominantly secretory IgA, isolated from a central wastewater treatment plant and building-scale wastewater collection points. These antibodies partition to the solids fraction and retain immunoaffinity for SARS-CoV-2 and Influenza A virus antigens. This stable pool could enable real-time tracking for correlates of vaccination, infection, and immunity, aiding in establishing population-level thresholds for immune protection and assessing the efficacy of future vaccine campaigns.

A Population-Based Study of SARS-CoV-2 IgG Antibody Responses to Vaccination in Manitoba.

Understanding variables that influence antibody responses to COVID-19 vaccination within a population can provide valuable information on future vaccination strategies. In this population-based study, we examined the antibody responses to COVID-19 vaccination in Manitoba using residual serum specimens collected between January 2021 and March 2022 (n = 20,365). Samples were tested for spike and nucleocapsid IgG against SARS-CoV-2 using clinically validated assays. We assessed the impacts of multiple factors on post-vaccination antibody titres including type of vaccine, age, sex, geographic location, number of doses received, and timing of vaccination. Our investigation demonstrated that vaccination with one dose of Moderna mRNA-1273 elicited higher anti-spike IgG titres overall compared to Pfizer BNT162b2 vaccination, while one dose of Pfizer BNT162b2 followed by a second dose of Moderna mRNA-1273 exhibited higher titres than two doses of Pfizer BNT162b2 or Moderna mRNA-1273, irrespective of age. Age and time post-vaccination had considerable effects on antibody responses, with older age groups exhibiting lower anti-spike IgG titres than younger ages, and titres of those vaccinated with Pfizer BNT162b2 waning faster than those vaccinated with Moderna mRNA-1273 or a combination of Pfizer BNT162b2 and Moderna mRNA-1273. Antibody titres did not appear to be affected by sex or geographic location. Our results identify how factors such as age and type of vaccine can influence antibody responses to vaccination, and how antibody titres wane over time. This information highlights the importance of tailoring vaccine regimens to specific populations, especially those at increased risk of severe COVID-19 and can be used to inform future vaccination strategies, scheduling of booster doses, and public health measures.

Sex differences in symptoms following the administration of BNT162b2 mRNA COVID-19 vaccine in children below 5 years of age in Germany (CoVacU5): a retrospective cohort study

BackgroundSex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany.MethodsThis is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3–10 µg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines.ResultsThe dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3 µg BNT162b2, no sex differences were noted, but after a first dose of 5–10 µg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15–1.55, p < 0.05) and general symptoms with OR 1.21 (95% CI: 1.01–1.44, p < 0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11–0.82, p < 0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms.ConclusionsSex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies (German Clinical Trials Register ID: DRKS00028759).

COVID-19 Vaccination and Vaccine Hesitancy in the Gaza Strip from a Cross-Sectional Survey in 2023: Prevalence, Risk Factors, and Associations with Health System Interventions.

Preventing COVID-19 in Gaza is crucial due to the devastation of advanced health services infrastructure by war. Despite the high protection offered by COVID-19 vaccines against severe disease, a 2021 survey in Gaza found only half of the population was vaccinated, and one-third was vaccine-hesitant. This follow-up study conducted in March 2023 aimed to re-evaluate vaccination levels, hesitancy, exposure to vaccine promotion efforts, and other risk factors in Gaza. A community-based cross-sectional survey with multistage stratified sampling was used. Associations of primary exposures and other determinants with vaccine status and hesitancy were quantified using bivariate and multivariable logistic regression. In 2023, 63.5% of adults received at least one vaccine dose compared to 49.1% in 2021 (p < 0.001). Vaccine hesitancy prevalence was 31.7% in 2023 versus 34.1% in 2021 (p = 0.395). Adjusted odds of vaccination were 4.2 times higher among those referred by health workers compared to those not referred. Adjusted odds of vaccine hesitancy among those who received information on the vaccine from health workers were 0.3 times that of people who did not receive information. Results suggest health workers could play a crucial role in future vaccination strategies, as their vaccine promotion efforts were linked to better vaccine outcomes. Investing in the skills development of community health workers to contribute to these efforts is recommended.

Changes in Attitudes towards Influenza and Pneumococcal Vaccination during the Subsiding COVID-19 Pandemic-Results of a Longitudinal Survey Study among Risk Groups in Germany between 2021 and 2023.

In many countries, an increase in influenza and pneumococcal vaccination rates was observed during the COVID-19 pandemic. We examined how attitude, risk perception and knowledge towards influenza and pneumococcal vaccines of at-risk patients developed when the COVID-19 pandemic subsided and if COVID-19 vaccination attitude (VA) was still associated with the attitudes towards the two other vaccines. We used longitudinal data from two surveys conducted in Germany in 2021 and 2023 among persons with chronic diseases. We assessed VA, risk perception, vaccination knowledge and further psychological determinants of vaccine acceptance. Structural equation modelling using full information maximum likelihood was used to estimate multivariate regressions with planned missing data. Among 543 respondents, the influenza and pneumococcal vaccination rates remained relatively stable between 2021 and 2023. VA also remained unchanged at a moderately positive level, while COVID-19 VA decreased. A constantly positive association between COVID-19 VA and influenza as well as pneumococcal VA was found, independent from a general VA. The perceived danger of influenza increased between 2021 and 2023 and was among the strongest predictors of influenza VA. Also at the subsiding pandemic, COVID-19 VA was constantly associated with the influenza and pneumococcal VA. It seems sensible to take these aspects into account when designing future vaccination campaigns for at-risk patients. DRKS00024561. Registered 9 March 2021.

TEMPORAL AND SPATIAL MODELING OF THE SPREAD OF DENGUE FEVER IN BRAZIL

Dengue is a viral infection caused by an arbovirus and spread through the bites of mosquitoes of the genus Aedes which causes significant human and economic damage every year. Preventive measures have been taken to reduce the proliferation of the transmitting mosquito and efforts are being made to obtain an efficient vaccine for the disease. Parallel to these measures, several studies present a model for the spread of the disease in order to determine relevant factors in the process and thus guide preventive measures and future vaccination initiatives. Within this context, this work brings a modeling for the spread of the disease through a system of differential equations where the geographic region studied (a Brazilian city) is divided into sub-regions with human circulation between them, thus making humans the spreader of the disease. Using the model, it was possible to characterize the time series of people infected with dengue in the city of Goiânia, Brazil, between 2000 and 2003 using two and three subdivisions of the geographic region studied. Seasonal cycles of the disease have been described without exhausting the number of susceptible humans.

An Application of an Initial Full Value of Vaccine Assessment Methodology to Measles-Rubella MAPs for Use in Low- and Middle-Income Countries.

Measles and rubella micro-array patches (MR-MAPs) are a promising innovation to address limitations of the current needle and syringe (N&S) presentation due to their single-dose presentation, ease of use, and improved thermostability. To direct and accelerate further research and interventions, an initial full value vaccine assessment (iFVVA) was initiated prior to MR-MAPs entering phase I trials to quantify their value and identify key data gaps and challenges. The iFVVA utilized a mixed-methods approach with rapid assessment of literature, stakeholder interviews and surveys, and quantitative data analyses to (i) assess global need for improved MR vaccines and how MR-MAPs could address MR problem statements; (ii) estimate costs and benefits of MR-MAPs; (iii) identify the best pathway from development to delivery; and (iv) identify outstanding areas of need where stakeholder intervention can be helpful. These analyses found that if MR-MAPs are broadly deployed, they can potentially reach an additional 80 million children compared to the N&S presentation between 2030-2040. MR-MAPs can avert up to 37 million measles cases, 400,000 measles deaths, and 26 million disability-adjusted life years (DALYs). MR-MAPs with the most optimal product characteristics of low price, controlled temperature chain (CTC) properties, and small cold chain volumes were shown to be cost saving for routine immunization (RI) in low- and middle-income countries (LMICs) compared to N&S. Uncertainties about price and future vaccine coverage impact the potential cost-effectiveness of introducing MR-MAPs in LMICs, indicating that it could be cost-effective in 16-81% of LMICs. Furthermore, this iFVVA highlighted the importance of upfront donor investment in manufacturing set-up and clinical studies and the critical influence of an appropriate price to ensure country and manufacturer financial sustainability. To ensure that MR-MAPs achieve the greatest public health benefit, MAP developers, vaccine manufacturers, donors, financiers, and policy- and decision-makers will need close collaboration and open communications.

Mechanism of enterovirus VP0 maturation cleavage based on the structure of a stabilised assembly intermediate.

Molecular details of genome packaging are little understood for the majority of viruses. In enteroviruses (EVs), cleavage of the structural protein VP0 into VP4 and VP2 is initiated by the incorporation of RNA into the assembling virion and is essential for infectivity. We have applied a combination of bioinformatic, molecular and structural approaches to generate the first high-resolution structure of an intermediate in the assembly pathway, termed a provirion, which contains RNA and intact VP0. We have demonstrated an essential role of VP0 E096 in VP0 cleavage independent of RNA encapsidation and generated a new model of capsid maturation, supported by bioinformatic analysis. This provides a molecular basis for RNA-dependence, where RNA induces conformational changes required for VP0 maturation, but that RNA packaging itself is not sufficient to induce maturation. These data have implications for understanding production of infectious virions and potential relevance for future vaccine and antiviral drug design.

The Evolution of Vaccines Development across Salmonella Serovars among Animal Hosts: A Systematic Review.

Salmonella is a significant zoonotic foodborne pathogen, and the global spread of multidrug-resistant (MDR) strains poses substantial challenges, necessitating alternatives to antibiotics. Among these alternatives, vaccines protect the community against infectious diseases effectively. This review aims to summarize the efficacy of developed Salmonella vaccines evaluated in various animal hosts and highlight key transitions for future vaccine studies. A total of 3221 studies retrieved from Web of Science, Google Scholar, and PubMed/Medline databases between 1970 and 2023 were evaluated. One hundred twenty-seven qualified studies discussed the vaccine efficacy against typhoidal and nontyphoidal serovars, including live-attenuated vaccines, killed inactivated vaccines, outer membrane vesicles, outer membrane complexes, conjugate vaccines, subunit vaccines, and the reverse vaccinology approach in different animal hosts. The most efficacious vaccine antigen candidate found was recombinant heat shock protein (rHsp60) with an incomplete Freund's adjuvant evaluated in a murine model. Overall, bacterial ghost vaccine candidates demonstrated the highest efficacy at 91.25% (95% CI = 83.69-96.67), followed by the reverse vaccinology approach at 83.46% (95% CI = 68.21-94.1) across animal hosts. More than 70% of vaccine studies showed significant production of immune responses, including humoral and cellular, against Salmonella infection. Collectively, the use of innovative methods rather than traditional approaches for the development of new effective vaccines is crucial and warrants in-depth studies.

A retrospective whole genome sequencing of SARS-CoV-2 isolate from respiratory sample of an individual from Ota – Ogun State, Nigeria

Severe acute respiratory syndrome coronavirus – 2 (SARS-CoV-2) which was responsible for the COVID-19 pandemic has now been considered an endemic virus, that will continually produce sporadic outbreaks in different communities around the globe. Although, there are several surveillance studies on SARS-CoV-2 globally, including Nigeria, there is still an important need to understand the uniqueness of the strains of the virus that was circulating immediately after the pandemic, to add to the global database of information that will aid vaccine production and future preparedness against another SARS - related CoV pandemic.Towards the end of the pandemic, between February – August 2022, SARS-CoV-2 was detected in a surveillance project in Ota – Ogun State Nigeria. We carried out a retrospective whole genome sequencing (WGS) analysis of SARS-CoV-2 in the previously reported positive sample, at Inqaba biotech in South Africa. RNA extraction was carried out using the Quick – RNA viral kit (Zymo) and library preparation was done by NEBNext ARTIC SARS-CoV-2 FS Library Prep kit (Illumina) according to the manufacturer's instruction. The WGS was carried out on the NextSeq500 platform by Illumina. The fastq file containing the unassembled raw sequence reads were submitted to NCBI SARS-CoV-2 resources, and a BioProject accession number PRJNA1076330 was issued. The DRAGEN Targeted Microbial, GISAID-CoVsurver mutation, BLAST and MAFFT applications were used for analysis.The spike (s) gene of the study sequence possessed seven mutations (G142D, A163V, V213G, D614G, H655Y, N679K, P681H) and shared 99.4 % identity with those of the Wuhan reference sequence WIV04. The non-structural proteins (NSP) – 7,8,9,10 and 16 shared 100 % identity with bat/Yunnan/RaTG13 (a SARS- related CoV found in bats) sequence on GISAID. Although, the study sequence was obtained from an asymptomatic individual, the S mutations observed are known to be related to virulence, antigenic shift, enhanced transmissibility and host change. Thus, upon successful exploitation of this asymptomatic variant, it may possibly be transformed to a potential candidate for SARS-CoV-2 vaccine in future.

Molecular epidemiology of Streptococcus pneumoniae isolates causing invasive and noninvasive infection in Ethiopia

Streptococcus pneumoniae, a medically important opportunistic bacterial pathogen of the upper respiratory tract, is a major public health concern, causing a wide range of pneumococcal illnesses, both invasive and noninvasive. It is associated with significant global morbidity and mortality, including pneumonia, meningitis, sepsis, and acute otitis media. The major purpose of this study was to determine the molecular epidemiology of Streptococcus pneumoniae strains that cause invasive and noninvasive infections in Ethiopia. A prospective study was undertaken in two regional hospitals between January 2018 and December 2019. Whole-genome sequencing was used to analyze all isolates. Serotypes and multilocus sequence types (MLST) were derived from genomic data. The E-test was used for antimicrobial susceptibility testing. Patient samples obtained 54 Streptococcus pneumoniae isolates, 33 from invasive and 21 from noninvasive specimens. Our findings identified 32 serotypes expressed by 25 Global Pneumococcal Sequence Clusters (GPSCs) and 42 sequence types (STs), including 21 new STs. The most common sequence types among the invasive isolates were ST3500, ST5368, ST11162, ST15425, ST15555, ST15559, and ST15561 (2/33, 6% each). These sequence types were linked to serotypes 8, 7 C, 15B/C, 16 F, 10 A, 15B, and 6 A, respectively. Among the noninvasive isolates, only ST15432, associated with serotype 23 A, had numerous isolates (4/21, 19%). Serotype 14 was revealed as the most resistant strain to penicillin G, whereas isolates from serotypes 3, 8, 7 C, and 10 A were resistant to erythromycin. Notably, all serotype 6 A isolates were resistant to both erythromycin and penicillin G. Our findings revealed an abnormally significant number of novel STs, as well as extremely diversified serotypes and sequence types, implying that Ethiopia may serve as a breeding ground for novel STs. Recombination can produce novel STs that cause capsular switching. This has the potential to influence how immunization campaigns affect the burden of invasive pneumococcal illness. The findings highlight the importance of continuous genetic surveillance of the pneumococcal population as a vital step toward enhancing future vaccine design.

Intranasal Self-Adjuvanted Lipopeptide Vaccines Elicit High Antibody Titers and Strong Cellular Responses against SARS-CoV-2.

Despite concerted efforts to tackle the COVID-19 pandemic, the persistent transmission of SARS-CoV-2 demands continued research into novel vaccination strategies to combat the virus. In light of this, intranasally administered peptide vaccines, particularly those conjugated to an immune adjuvant to afford so-called "self-adjuvanted vaccines", remain underexplored. Here, we describe the synthesis and immunological evaluation of self-adjuvanting peptide vaccines derived from epitopes of the spike glycoprotein of SARS-CoV-2 covalently fused to the potent adjuvant, Pam2Cys, that targets toll-like receptor 2 (TLR2). When administered intranasally, these vaccines elicited a strong antigen-specific CD4+ and CD8+ T-cell response in the lungs as well as high titers of IgG and IgA specific to the native spike protein of SARS-CoV-2. Unfortunately, serum and lung fluid from mice immunized with these vaccines failed to inhibit viral entry in spike-expressing pseudovirus assays. Following this, we designed and synthesized fusion vaccines composed of the T-cell epitope discovered in this work, covalently fused to epitopes of the receptor-binding domain of the spike protein reported to be neutralizing. While antibodies elicited against these fusion vaccines were not neutralizing, the T-cell epitope retained its ability to stimulate strong antigen-specific CD4+ lymphocyte responses within the lungs. Given the Spike(883-909) region is still completely conserved in SARS-CoV-2 variants of concern and variants of interest, we envision the self-adjuvanting vaccine platform reported here may inform future vaccine efforts.

A Serum Multi-Parametric Analysis Identifies an Early Innate Immune Signature Associated to Increased Vaccine-Specific Antibody Production and Seroconversion in Simultaneous COVID-19 mRNA and Cell-Based Quadrivalent Influenza Vaccination.

In this pilot study, a multi-parametric analysis comparing immune responses in sera of adult healthy subjects (HS) or people with type 2 diabetes mellitus (T2D) undergoing the single or simultaneous administration of mRNA-based COVID-19 and cellular quadrivalent inactivated influenza vaccines was conducted. While SARS-CoV-2 antibodies remains comparable, influenza antibody titers and seroconversion were significantly higher upon simultaneous vaccination. Magnitude of anti-influenza humoral response closely correlated with an early innate immune signature, previously described for the COVID-19 vaccine, composed of IL-15, IL-6, TNF-α, IFN-γ, CXCL-10 and here extended also to acute-phase protein Pentraxin 3. People with T2D receiving simultaneous vaccination showed a protective response comparable to HS correlating with the early induction of IFN-γ/CXCL10 and a significant reduction of the circulating glucose level due to increased oxidation of glucose digestion and consumption. These data, although preliminary and in-need of validation in larger cohorts, might be exploited to optimize future vaccination in people with chronic disorders, including diabetes.

Planning and adjusting the COVID-19 booster vaccination campaign to reduce disease burden

As public health policies shifted in 2023 from emergency response to long-term COVID-19 disease management, immunization programs started to face the challenge of formulating routine booster campaigns in a still highly uncertain seasonal behavior of the COVID-19 epidemic. Mathematical models assessing past booster campaigns and integrating knowledge on waning of immunity can help better inform current and future vaccination programs. Focusing on the first booster campaign in the 2021/2022 winter in France, we used a multi-strain age-stratified transmission model to assess the effectiveness of the observed booster vaccination in controlling the succession of Delta, Omicron BA.1 and BA.2 waves. We explored counterfactual scenarios altering the eligibility criteria and inter-dose delay. Our study showed that the success of the immunization program in curtailing the Omicron BA.1 and BA.2 waves was largely dependent on the inclusion of adults among the eligible groups, and was highly sensitive to the inter-dose delay, which was changed over time. Shortening or prolonging this delay, even by only one month, would have required substantial social distancing interventions to curtail the hospitalization peak. Also, the time window for adjusting the delay was very short. Our findings highlight the importance of readiness and adaptation in the formulation of routine booster campaign in the current level of epidemiological uncertainty.