Enhance Vaccine Responses Research Articles

Systemic dysregulation and molecular insights into poor influenza vaccine response in the aging population.

Vaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of systemic dysregulation in poor responders. Multiomics integration revealed key molecules and their likely role in vaccination response. High prevaccination plasma interleukin-15 (IL-15) concentrations negatively associated with antibody production, further supported by experimental validation in mice revealing an IL-15-driven natural killer cell axis explaining the suppressive role in vaccine-induced antibody production as observed in poor responders. We propose a subset of long-chain fatty acids as modulators of persistent inflammation in poor responders. Our findings provide a potential link between low-grade chronic inflammation and poor vaccination response and open avenues for possible pharmacological interventions to enhance vaccine responses.

Exploring the associations between gut microbiota composition and SARS-CoV-2 inactivated vaccine response in mice with type 2 diabetes mellitus.

Over 7 million deaths attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by 6 May 2024 underscore the urgent need for effective vaccination strategies. However, individuals with type 2 diabetes mellitus (T2DM) have been identified as particularly vulnerable and display compromised immune responses to vaccines. Concurrently, increasing evidence suggests that the composition and diversity of gut microbiota, crucial regulators of immune function, may influence the efficacy of vaccines. Against this backdrop, our study explores the complex interplay among SARS-CoV-2 inactivated vaccination, T2DM, and host microbiota. We discover that T2DM compromises the initial immune response to the SARS-CoV-2 inactivated vaccine, and this response is positively correlated with specific features of the gut microbiota, such as alpha diversity. We also demonstrate that the vaccination itself induces alterations in the composition and structure of the gut microbiota. These findings illuminate potential links between the gut microbiota and vaccine efficacy in individuals with T2DM, offering valuable insights that could enhance vaccine responses in this high-risk population.

Human Milk Oligosaccharides in Combination with Galacto- and Long-Chain Fructo-Oligosaccharides Enhance Vaccination Efficacy in a Murine Influenza Vaccination Model.

Early-life nutrition significantly impacts vaccination efficacy in infants, whose immune response to vaccines is weaker compared to adults. This study investigated vaccination efficacy in female C57Bl/6JOlaHsd mice (6 weeks old) fed diets with 0.7% galacto-oligosaccharides (GOS)/long-chain fructo-oligosaccharides (lcFOS) (9:1), 0.3% human milk oligosaccharides (HMOS), or a combination (GFH) for 14 days prior to and during vaccination. Delayed-type hypersensitivity (DTH) was measured by assessing ear swelling following an intradermal challenge. Influvac-specific IgG1 and IgG2a levels were assessed using ELISAs, while splenic T and B lymphocytes were analyzed for frequency and activation via flow cytometry. Additionally, cytokine production was evaluated using murine splenocytes co-cultured with influenza-loaded dendritic cells. Mice on the GFH diet showed a significantly enhanced DTH response (p < 0.05), increased serological IgG1 levels, and a significant rise in memory B lymphocytes (CD27+ B220+ CD19+). GFH-fed mice also exhibited more activated splenic Th1 cells (CD69+ CXCR3+ CD4+) and higher IFN-γ production after ex vivo restimulation (p < 0.05). These findings suggest that GOS/lcFOS and HMOS, particularly in combination, enhance vaccine responses by improving memory B cells, IgG production, and Th1 cell activation, supporting the potential use of these prebiotics in infant formula for better early-life immune development.

From hit to vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation.

Vaccination can help prevent infection and can also be used to treat cancer, allergy, and potentially even drug overdose. Adjuvants enhance vaccine responses, but currently, the path to their advancement and development is incremental. We used a phenotypic small-molecule screen using THP-1 cells to identify nuclear factor-κB (NF-κB)-activating molecules followed by counterscreening lead target libraries with a quantitative tumor necrosis factor immunoassay using primary human peripheral blood mononuclear cells. Screening on primary cells identified an imidazopyrimidine, dubbed PVP-037. Moreover, while PVP-037 did not overtly activate THP-1 cells, it demonstrated broad innate immune activation, including NF-κB and cytokine induction from primary human leukocytes in vitro as well as enhancement of influenza and SARS-CoV-2 antigen-specific humoral responses in mice. Several de novo synthesis structural enhancements iteratively improved PVP-037's in vitro efficacy, potency, species-specific activity, and in vivo adjuvanticity. Overall, we identified imidazopyrimidine Toll-like receptor-7/8 adjuvants that act in synergy with oil-in-water emulsion to enhance immune responses.

Morning administration enhances humoral response to SARS-CoV-2 vaccination in kidney transplant recipients

Although severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid (SARS-CoV-2 mRNA) vaccines are effective in kidney transplant recipients (KTRs), their immune response to vaccination is blunted by immunosuppression. Other tools enhancing vaccination response are therefore needed. Interestingly, aligning vaccine administration with circadian rhythms (chronovaccination) has been shown to boost immune response. However, its applicability in KTRs, whose circadian rhythms are likely disrupted by immunosuppressants, remains unclear. To assess the impact of vaccination timing on seroconversion in the KTRs population, we analyzed data from 553 virus-naïve KTRs who received 2 doses of messenger ribonucleic acid (mRNA) vaccine. Bayesian logistic regression was employed, adjusting for previously identified predictors of seroconversion, including allograft function, maintenance immunosuppressants, or time since transplantation. SARS-CoV-2 immunoglobulin G (IgG) levels were measured with a median of 47 days after the second dose. The results did not reveal a reliable effect of timing of the first dose but did indicate that earlier timing for the second dose brings a notable benefit—every 1-hour delay in the application was associated with a 16% reduction in the odds of seroconversion (OR 0.84, 95% CI 0.71, 0.998). Similar results were obtained from quantile regression modeling IgG levels. In conclusion, morning vaccination is emerging as a promising and easily implementable strategy to enhance vaccine response in KTRs.

The receptor binding domain of SARS-CoV-2 Omicron subvariants targets Siglec-9 to decrease its immunogenicity by preventing macrophage phagocytosis.

The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response.

Circularized Nanodiscs for Multivalent Mosaic Display of SARS-CoV-2 Spike Protein Antigens

The emergence of vaccine-evading SARS-CoV-2 variants urges the need for vaccines that elicit broadly neutralizing antibodies (bnAbs). Here, we assess covalently circularized nanodiscs decorated with recombinant SARS-CoV-2 spike glycoproteins from several variants for eliciting bnAbs with vaccination. Cobalt porphyrin–phospholipid (CoPoP) was incorporated into the nanodisc to allow for anchoring and functional orientation of spike trimers on the nanodisc surface through their His-tag. Monophosphoryl-lipid (MPLA) and QS-21 were incorporated as immunostimulatory adjuvants to enhance vaccine responses. Following optimization of nanodisc assembly, spike proteins were effectively displayed on the surface of the nanodiscs and maintained their conformational capacity for binding with human angiotensin-converting enzyme 2 (hACE2) as verified using electron microscopy and slot blot assay, respectively. Six different formulations were prepared where they contained mono antigens; four from the year 2020 (WT, Beta, Lambda, and Delta) and two from the year 2021 (Omicron BA.1 and BA.2). Additionally, we prepared a mosaic nanodisc displaying the four spike proteins from year 2020. Intramuscular vaccination of CD-1 female mice with the mosaic nanodisc induced antibody responses that not only neutralized matched pseudo-typed viruses, but also neutralized mismatched pseudo-typed viruses corresponding to later variants from year 2021 (Omicron BA.1 and BA.2). Interestingly, sera from mosaic-immunized mice did not effectively inhibit Omicron spike binding to human ACE-2, suggesting that some of the elicited antibodies were directed towards conserved neutralizing epitopes outside the receptor binding domain. Our results show that mosaic nanodisc vaccine displaying spike proteins from 2020 can elicit broadly neutralizing antibodies that can neutralize mismatched viruses from a following year, thus decreasing immune evasion of new emerging variants and enhancing healthcare preparedness.

Additional Burden Averted in the United States From Use of MF59-Adjuvanted Seasonal Influenza Vaccine Compared With Standard Seasonal Influenza Vaccine Among Adults ≥65 Years.

The MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3) is designed to overcome immunosenescence and enhance vaccine responses in older adults. We expanded on the Centers for Disease Control and Prevention (CDC) modeling method to estimate the number of additional influenza-related outcomes averted with aIIV3 versus generic quadrivalent inactivated influenza vaccine (IIV4) in adults ≥65 years over 3 influenza seasons (2017-2018 to 2019-2020) in the United States. A static compartmental model was developed based on an existing CDC model with 2 previously recommended calculation methods that increased the accuracy of the model in providing estimates of burden averted. Model inputs included vaccine effectiveness, vaccine coverage, population counts, and disease burden estimates. Additional burden averted (symptomatic cases, outpatient visits, hospitalizations, intensive care unit [ICU] admissions, and deaths) was expressed as total incremental cases averted between the vaccines. Sensitivity analyses tested the resilience of the model results to uncertainties in model inputs. The model estimated that vaccination with aIIV3 versus IIV4 would avert 2.24 times as many symptomatic cases, outpatient visits, hospitalizations, ICU stays, and deaths during 2017-2018; the burden averted in 2018-2019 and 2019-2020 with aIIV3 would be 3.44 and 1.72 times that averted with IIV4, respectively. Disease burden estimates and relative vaccine effectiveness of aIIV3 had the greatest impact on model estimates. Over 3 influenza seasons, the model estimated that aIIV3 was more effective than IIV4 in averting influenza-related outcomes, preventing 1.72 to 3.44 times as many influenza illnesses with proportionate decreases in related healthcare use and complications.

Sialophorin is an essential host element for vaccine immunity against pulmonary fungal infections

Abstract The global incidence of fungal infections is alarming due to the increasing immunocompromised population. Vaccine measures are necessary to prevent fungal diseases. Identifying a protective host element as a functional phenotypic marker is immensely valuable as a target to enhance vaccine responses, measure vaccine efficacy, and assess disease outcomes. We identified a host element, O-glycosylated sialophorin, preferentially associated with antifungal memory Tc17 (IL-17A +) cells. Using a mouse model of fungal vaccine immunity during CD4 +T-cell deficiency, we found that sialophorin was essential to bolster vaccine-induced CD8 +T-cell responses and immunity to pulmonary infection. Sialophorin-sufficient CD8 +T cells were superior in responses than the deficient cells under a similar inflammatory micromilieu. Supplementation of sialophorin mAb that binds to O-glycosylated form potentiated the CD8 +T cell responses to fungal antigens, and an inhibitory mAb that binds to non-O-glycosylated form selectively reduced Tc1 (IFNγ +) but not Tc17 cell responses. Sialophorin-mediated immunity was independent of T cell trafficking into the lung. Finally, using fungal antigens vaccination, we show that O-glycosylated sialophorin is a marker of vaccine-potency and immunity. Our study revealed that sialophorin is an essential host element to bolster vaccine responses and serves as a potential biomarker of fungal immunity. NIAID-NIH 5R01AI153522

2141. Investigating a (Natural) Killer by Studying the Victims: Searching for Mechanisms to Selectively Inhibit NK-cell Immunosuppressive Function to Improve Vaccine Responses

Abstract Background Decades of effort have yet to deliver an efficacious vaccine for pathogens such as HIV, despite major revelations about HIV antigens and development of new vaccine platforms. Innovative outside-the-box approaches are needed to overcome immunological roadblocks to the success of past and current vaccine regimens. We discovered that natural killer (NK) cells are a potent obstacle to vaccine success through perforin-dependent suppression of activated CD4 T cell responses early after vaccination. This killing reduces the quantity and quality of antibody responses. Yet, the features of NK cells that enable this activity or determine susceptibility of specific subsets of T cells remain ill-defined. Methods We used transgenic virus-specific mouse CD4 T cells to detect very early changes in responding T cells immediately proximal to immunoregulatory killing by NK cells. Transgenic T cells were seeded in recipient mice, depleted or not of NK cells, and then infected with lymphocytic choriomeningitis virus. At early time points post-infection, these T cells were isolated for single-cell RNA-sequencing or high-dimensional flow cytometry analyses. These data revealed transcriptomic and proteomic features of subsets of activated CD4 T cells whose presence was enabled or enhanced by the absence of NK cells. Results Perforin-dependent killing of CD4 T cells by NK cells is measurable on days 2 and 3 post-infection. Analysis of the pool of responding T cells on day 3 revealed phenotypic skewing away from follicular helper T cell-type responses to Th1-type responses in the presence of NK cells. Single cell RNA sequencing and high-dimensional spectral flow cytometry reveal clusters of T cells that are markedly enriched in the absence of NK cells. Conclusion We created a model system permitting characterization of the population of T cells targeted by NK cells after infection or immunization. Elucidation of features of the targeted T cells will provide mechanistic insights in the receptor-ligand system enabling this biology, improve our understanding of how NK cells influence the pool of responding T cells, and facilitate discovery of the corresponding subset of NK cells responsible for this activity. These discoveries are likely to facilitate development of methods to enhance vaccine responses. Disclosures All Authors: No reported disclosures.

Booster and Btki Interruption Improve Response to Sars-Cov-2 Vaccine in Patients with CLL

Introduction: Patients with chronic lymphocytic leukemia (CLL) have inadequate responses to vaccination, including SARS-CoV-2 mRNA vaccines. Treatment with anti-B cell therapies, such as anti-CD20 monoclonal antibodies (mAb) and Bruton's tyrosine kinase inhibitors (BTKi), further suppress the antibody (Ab) response to vaccines. We investigated whether BTKi interruption around the time of a booster injection could enhance vaccine response. Methods: A single-institution retrospective cohort study of patients with CLL was conducted at the National Institutes of Health from 2020-2022. Treatment naïve (TN) patients as well as those receiving treatment with a BTKi or venetoclax (VEN) were included. Patients who received IVIG, anti-SARS-CoV-2 mAb, or convalescent plasma within three months of vaccination were excluded. Anti-spike Ab titers were measured after completion of the primary series (2 doses of Pfizer-BioNTech/Moderna vaccines or 1 dose of Janssen vaccine) and the first booster. Ab titers were measured using the Roche Elecsys® immunoassay and categorized as no response (<0.8 U/mL), weak response (0.8-50 U/mL), or strong response (>50 U/mL). Ultra-deep TCRβ sequencing (Adaptive Biotechnologies) was performed before and after the primary series to identify and track spike-specific clonotypes. A T-cell vaccine response was defined as significant expansion of ≥1 spike-specific clonotype. Results: We studied Ab response in 86 patients (54 on BTKi, 14 on VEN, and 18 TN). The median age was 68.0 (range 66-69) and 97.7% of patients received mRNA vaccine. After the primary series, seroconversion (anti-spike Ab ≥0.8 U/mL) was detected in 53% of BTKi-treated patients, 57% of patients on single-agent VEN, and 67% of TN patients. After booster, anti-spike Ab was detected in 87% of BTKi-treated patients, 50% of patients on single-agent VEN, and 83% of TN patients. No patients who received anti-CD20 mAb within 12 months of vaccination (in combination with VEN) responded to the primary series or booster. All patients with seroconversion post primary series also had detectable anti-spike Ab post booster. Anti-spike Ab increased after booster in 90% of patients who responded to the primary series. Of the patients who did not respond to the primary series, 57% seroconverted post booster. Seroconversion was associated with higher serum IgM after the primary series (median 37g/L (IQR 24-63) vs. 26g/L (IQR 9-37), p=0.02) as well as higher serum IgG (median 848g/L (IQR 620-920) vs. 611g/L (IQR 395-782), p=0.02). Patients with detectable anti-spike Ab after booster had higher IgM (median 35g/L (IQR 22-65) vs. 9g/L (IQR 5-437), p=0.04) as well as higher IgA (median 88g/L (IQR 65-112) vs. 41g/L (IQR14-84), p=0.01). Of patients on BTKi, 21/40 (52%) had seroconversion after the primary series, albeit with mostly weak responses (62%). After booster, 34/40 (85%) had detectable anti-spike Ab. Of BTKi-treated patients with a weak response to the primary series, 10/13 (77%) mounted a strong response to booster. Twelve patients interrupted BTKi for a median of 21 days (range 8-22) around the time of booster. Patients who interrupted BTKi had higher anti-spike Ab (median 7,149 U/mL, IQR 1109-19900) than those who continued therapy (median 1,198 U/mL, IQR 2.05-2985, p=0.02). Three patients experienced lymph node pain and swelling during BTKi interruption and resumed BTKi earlier than intended. Longitudinal analysis of Ab titers post-booster among BTKi patients demonstrated a decline in anti-spike Ab of 0.45% per day, which denotes a 50% decline in 111 days. No difference in the rate of decline was observed between patients who interrupted BTKi and those who continued BTKi. T-cell response to the primary series was observed in 7/15 (47%) of BTKi-treated patients. No significant difference in T-cell response was found between patients on ibrutinib and those on acalabrutinib (p=0.6). T-cell response after the primary series was not predictive of Ab response post-booster (p=0.3). Conclusion: Increasing anti-spike Ab with subsequent vaccinations support additional boosters in patients with CLL. BTKi interruption at the time of vaccination results in a more robust Ab response.

Discontinuing methotrexate to enhance vaccine response.

In patients with autoimmune rheumatic disease, methotrexate therapy has been associated with poor immune response to vaccines, including those intended to provide protection against COVID-19. Emerging evidence supports the practice of temporarily discontinuing this treatment in order to improve immunogenicity.

Time of day of vaccination does not relate to antibody response to thymus-independent vaccinations

Variable responses to vaccination are of historical and current concern, particularly among vulnerable groups. Biochemical and behavioural methods of improving vaccination response have been examined. There is some evidence that vaccinating in the morning could enhance vaccine responses, however, this has consistently been shown in thymus-dependent vaccinations, such as influenza. The present analysis of data from two observational studies of the association between psychosocial factors and vaccination response. These data included response to a thymus-independent vaccination - pneumococcal polysaccharide vaccine, examined morning versus afternoon vaccine administration in 75 healthy young adults and 61 parents, including 32 caregivers of a child with a development disability and 29 control parents. In both datasets, timing of vaccination was not related to antibody response. This suggests that effects of time of day may be limited to thymus-dependent vaccinations although replication in a large randomised controlled trial using other thymus-dependent vaccinations is required.

Effects of 3 months of multi-nutrient supplementation on the immune system and muscle and respiratory function of older adults in aged care (The Pomerium Study): protocol for a randomised controlled trial

IntroductionImmunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with SARS-CoV-2 (COVID-19),...

Micronutrients to Support Vaccine Immunogenicity and Efficacy.

The world has entered the third year of the coronavirus disease 2019 (COVID-19) pandemic. Vaccination is the primary public health strategy to protect against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in addition to other measures, such as mask wearing and social distancing. Vaccination has reduced COVID-19 severity and mortality dramatically. Nevertheless, incidence globally remains high, and certain populations are still at risk for severe outcomes. Additional strategies to support immunity, including potentially enhancing the response to vaccination, are needed. Many vitamins and trace minerals have recognized immunomodulatory actions, and their status and/or supplementation have been reported to correspond to the incidence and severity of infection. Furthermore, a variety of observational and some interventional studies report that adequate micronutrient status or micronutrient supplementation is associated with enhanced vaccine responses, including to COVID-19 vaccination. Such data suggest that micronutrient supplementation may hold the potential to improve vaccine immunogenicity and effectiveness, although additional interventional studies to further strengthen the existing evidence are needed. Positive findings from such research could have important implications for global public health, since deficiencies in several micronutrients that support immune function are prevalent in numerous settings, and supplementation can be implemented safely and inexpensively.

The Negative Effect of Preexisting Immunity on Influenza Vaccine Responses Transcends the Impact of Vaccine Formulation Type and Vaccination History.

The most effective measure to induce protection from influenza is vaccination. Thus, yearly vaccination is recommended, which, together with infections, establishes diverse repertoires of B cells, antibodies, and T cells. We examined the impact of this accumulated immunity on human responses in adults to split, subunit, and recombinant protein-based influenza vaccines. Enzyme-linked immunosorbent assay (ELISA) assays, to quantify serum antibodies, and peptide-stimulated CD4 T-cell cytokine ELISpots revealed that preexisting levels of hemagglutinin (HA)-specific antibodies were negatively associated with gains in antibody postvaccination, while preexisting levels of CD4 T cells were negatively correlated with vaccine-induced expansion of CD4 T cells. These patterns were seen independently of the vaccine formulation administered and the subjects' influenza vaccine history. Thus, although memory CD4 T cells and serum antibodies consist of components that can enhance vaccine responses, on balance, the accumulated immunity specific for influenza A H1 and H3 proteins is associated with diminished future responses.

Cutaneous CpG adjuvant conditioning to enhance vaccine responses

Adjuvant activity of the Toll receptor 9 agonist CpG 1826 was compared when given subcutaneously (s.c.) together with ovalbumin (s.c.[CpG + Ova]), or when given by either s.c. or intradermally (i.d.) routes two days prior to s.c. ovalbumin. Frequencies of CD8 + effector (TEFF) and central memory (TCM) T cells along with total IgG, IgG2c, and IgG1 titres were measured to ascertain how timing and location of CpG conditioning influenced vaccination outcome. Prior treatment with CpG enhanced TEFF, TCM, as well as total IgG responses. TEFF and TCM responses were greatest when CpG was given intradermally and prior to s.c. ovalbumin, conditions that eliminated the fraction of TCM ‘non-responders’ observed after s.c.[CpG + Ova] vaccination. IgG responses were polarized toward IgG2c after early s.c. CpG but toward IgG1 after early i.d. CpG. Separating CpG adjuvant and antigen application in time and space can improve vaccination outcome.

Vaccine Interactions With the Infant Microbiome: Do They Define Health and Disease?

Over the past decade, there has been a growing awareness of the vital role of the microbiome in the function of the immune system. Recently, several studies have demonstrated a relationship between the composition of the microbiome and the vaccine-specific immune response. As a result of these findings, the administration of probiotics has been proposed as a means of boosting vaccine-specific immunity. Early results have so far been highly inconsistent, with little evidence of sustained benefit. To date, a precise determination of the aspects of the microbiome that impact immunity is still lacking, and the mechanisms of action are also unknown. Further investigations into these questions are necessary to effectively manipulate the microbiome for the purpose of boosting immunity and enhancing vaccine-specific responses in infants. In this review, we summarize recent studies aimed at altering the neonatal gut microbiome to enhance vaccine responses and highlight gaps in knowledge and understanding. We also discuss research strategies aimed at filling these gaps and developing potential therapeutic interventions.

Targeting Inflammation and Immunosenescence to Improve Vaccine Responses in the Elderly

One of the most appreciated consequences of immunosenescence is an impaired response to vaccines with advanced age. While most studies report impaired antibody responses in older adults as a correlate of vaccine efficacy, it is now widely appreciated that this may fail to identify important changes occurring in the immune system with age that may affect vaccine efficacy. The impact of immunosenescence on vaccination goes beyond the defects on antibody responses as T cell-mediated responses are reshaped during aging and certainly affect vaccination. Likewise, age-related changes in the innate immune system may have important consequences on antigen presentation and priming of adaptive immune responses. Importantly, a low-level chronic inflammatory status known as inflammaging has been shown to inhibit immune responses to vaccination and pharmacological strategies aiming at blocking baseline inflammation can be potentially used to boost vaccine responses. Yet current strategies aiming at improving immunogenicity in the elderly have mainly focused on the use of adjuvants to promote local inflammation. More research is needed to understand the role of inflammation in vaccine responses and to reconcile these seemingly paradoxical observations. Alternative approaches to improve vaccine responses in the elderly include the use of higher vaccine doses or alternative routes of vaccination showing only limited benefits. This review will explore novel targets and potential new strategies for enhancing vaccine responses in older adults, including the use of anti-inflammatory drugs and immunomodulators.

Underimmunization of the solid organ transplant population: An urgent problem with potential digital health solutions.

Solid organ transplant recipients are at risk for potentially life-threatening infections due to lifelong immunosuppression. Vaccine-preventable infections result in graft injury, morbidity, mortality, and significantly increased medical costs. Unfortunately, the majority of transplant recipients continue to be underimmunized at the time of transplant and thereafter. Given the rising rates of vaccine hesitancy and refusal in the general population, transplant recipients can no longer rely on herd immunity to protect them from vaccine-preventable infections. Novel tools are desperately needed to overcome transplant-specific immunization barriers to improve immunization rates in this high-risk population. Digital health technologies may offer a solution by addressing transplant-specific barriers: specifically, providing accurate information about vaccine safety, efficacy, and timing in the pre- and posttransplant periods; making a complete immunization record universally available and easily accessible; enabling communication between patients and multiple providers; and providing automated vaccine reminders to both patients and providers when vaccines are due using transplant-specific immunization guidelines. Digital health has transformed health care by empowering patients with their own health information and connecting patients, their providers, and public health officials. In doing so, it offers a potential platform to address and overcome the problem of underimmunization in the transplant population.