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Navigating acceptance: challenges and barriers to Nipah virus vaccine uptake in Malaysia's muslim-majority context.

INTRODUCTION: The development of Nipah virus (NiV) vaccine offers a vital opportunity for pandemic preparedness in Southeast Asia, especially in Malaysia, where the first outbreak occurred. However, vaccine acceptance must be understood within diverse cultural, religious, and social contexts. AREAS COVERED: This review explores key challenges and barriers to NiV vaccine uptake among Malaysia's Muslim-majority population, drawing insights from past rollouts such as COVID-19 and HPV vaccines. Key issues include religious concerns, misinformation, historical hesitancy, lack of trust in health authorities, and gaps in knowledge, attitudes, and perceptions, which collectively hinder vaccine acceptance and uptake. The paper also highlights enablers namely religious endorsements, transparent communication, and culturally sensitive engagement with trusted healthcare and community leaders. Evidence-based strategies, like motivational interviewing, narrative communication, and tailored outreach, are discussed. Finally, the 7C model is introduced as a structured framework to address behavioral and psychological barriers to vaccination. EXPERT OPINION: Research gaps remain in understanding local psychological drivers, religious governance dynamics, and misinformation patterns. Future efforts should prioritize nationwide KAP studies, validation of behavioral frameworks such as the 7C model, and interventional research on culturally tailored communication. Integrating early halal certification and coordinated religious engagement will be essential for effective and equitable uptake.

Humans

Electronic Nudges to Increase Influenza Vaccination in Immunosuppressed Adults Across the Age Spectrum: A Pooled Analysis of 2 Nationwide Randomized Trials.

BACKGROUND: Immunosuppressed individuals face higher risk of severe influenza complications, yet vaccination coverage remains low. We aimed to assess the effect of electronic letter-based nudges on influenza vaccination uptake by immunosuppression status. METHODS: We performed a participant-level pooled analysis of 2 methodologically harmonized, nationwide, pragmatic randomized clinical trials during the 2023-2024 influenza season. Adults aged &#x2265;65 years (NUDGE-FLU-2) and adults aged 18-64 years with chronic conditions (NUDGE-FLU-CHRONIC) were included, with immunosuppression defined by an immunosuppressive diagnosis or a filled prescription for immunosuppressive therapy. Participants were randomized in a 2.45:1:1:1:1:1:1 ratio to usual care or 1 of 6 electronic letter interventions. The primary outcome was receipt of influenza vaccination by 1 January 2024 ascertained from nationwide administrative health registries. Effect modification by immunosuppression status was assessed using binomial regression. RESULTS: Among 1 181 254 participants (mean age 67 years; 73 830 [6.3%] immunosuppressed), 66.1% were vaccinated. Any letter increased vaccine uptake compared with usual care (absolute difference, 2.79% points; 95% confidence interval [CI], 2.60-2.98; P < .001), with greater effect among immunosuppressed individuals (+4.12 vs +2.70% points; Pinteraction = .002). In younger adults with chronic conditions, letter-based nudges increased vaccination rates by 11.7% points overall and by 13.3% points among those with immunosuppression (Pinteraction = .007). Among immunosuppressed individuals, nudging effects appeared greater for those with immunosuppressive conditions than for those receiving immunosuppressive treatment. CONCLUSIONS: Electronic letter-based nudges increased influenza vaccination rates, with greater benefit among immunosuppressed individuals. These findings support implementation of low-cost, letter-based nudging strategies to improve vaccine uptake in this high-risk population. Clinical Trials Registration. NCT06030726 and NCT06030739.

Adolescent

Vaccine preferences and their role for vaccine confidence and uptake: a meta-ethnography.

Vaccine confidence and uptake are influenced by individuals' preferences regarding vaccine composition, quality, or administration pathways. However, literature synthesizing available qualitative insights into individuals' vaccine preferences remains limited. We therefore conducted a meta-ethnographic systematic review of the qualitative literature on vaccine preferences to identify opportunities for enhancing vaccine confidence and uptake. We implemented a comprehensive search strategy and screened 5,528 studies across seven research databases published between 2001 and 2023. We identified and synthesized 97 qualitative articles to delineate factors influencing consumers' vaccine preferences. Our findings revealed four primary domains shaping individuals' vaccine preferences: Product, Place, Price, and Promotion. First, individuals' preferences for vaccines often hinge on perceived quality and safety of the product itself, which can, for example, be associated with vaccine brand or origin, especially in the case of novel vaccines. Second, people prioritize convenience in terms of vaccination sites and delivery methods (wanting vaccinations offered at their doorstep or in local peripheral clinics); evidence regarding preferred groups to administer the vaccines was mixed. Third, the price of vaccines and the secondary costs associated with vaccination played a role in uptake considerations. Finally, both the sources of information (such as healthcare workers, community volunteers, and religious authorities) and the methods of promoting vaccine information (including face-to-face consultations during clinic visits and the distribution of leaflets or banners), emerged as crucial factors shaping decision-making processes. Overall findings highlight the importance of addressing multifaceted preferences to enhance vaccine confidence and uptake. By understanding individuals' vaccine preferences, strategic recommendations can be developed to optimize vaccination programs and ensure acceptability and utilization.

Humans

Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA.

While SARS-CoV-2 vaccines have shown strong efficacy, the continued emergence of new viral variants raises concerns about the ongoing and future public health impact of COVID-19, especially in locations with suboptimal vaccination uptake. We investigated viral and host factors, including vaccination status, that were associated with SARS-CoV-2 disease severity in a setting with low vaccination rates. We analyzed clinical and demographic data from 1,957 individuals in the state of Georgia, USA, coupled with viral genome sequencing from 1,185 samples. We found no specific mutations associated with disease severity. Compared to those who were unvaccinated, vaccinated individuals experienced less severe SARS-CoV-2 disease, and the effect was similar for both variants. Vaccination within the prior 3-9 months was associated with decreased odds of moderate disease, severe disease, and death. Older age and underlying health conditions, especially immunosuppression and renal disease, were associated with increased disease severity. Overall, this study provides insights into the impact of vaccination status, variants/mutations, and clinical factors on disease severity in SARS-CoV-2 infection when vaccination rates are low. Understanding these associations will help refine and reinforce messaging around the crucial importance of vaccination in mitigating the severity of SARS-CoV-2 disease.

Humans

Respiratory Syncytial Virus Disease Burden and Nirsevimab Effectiveness in Young Children From 2023-2024.

IMPORTANCE: During the 2023-2024 respiratory syncytial virus (RSV) season in the United States, 2 new RSV prevention products were recommended to protect infants in their first RSV season: nirsevimab and Pfizer's maternal RSV vaccine. Postlicensure studies are needed to assess prevention product impact and effectiveness. OBJECTIVE: To compare the epidemiology and disease burden of medically attended RSV-associated acute respiratory illness (ARI) among children younger than 5 years during the 2023-2024 RSV season with 3 prepandemic RSV seasons (2017-2020), estimate nirsevimab effectiveness against medically attended RSV-associated ARI, and compare nirsevimab binding site mutations among circulating RSV in infants with and without nirsevimab receipt. DESIGN, SETTING, AND PARTICIPANTS: This study included prospective population-based surveillance for medically attended ARI with systematic molecular testing for RSV and whole-genome sequencing of RSV positive samples, as well as a test-negative case-control design to estimate nirsevimab effectiveness. The study was conducted in 7 academic pediatric medical centers in the United States with data from RSV seasons (September 1 through April 30) in 2017 through 2020. Participants were children younger than 5 years with medically attended ARI. EXPOSURE: For the nirsevimab effectiveness analyses, nirsevimab receipt among infants younger than 8 months as of or born after October 1, 2023. MAIN OUTCOME AND MEASURE: Medically attended RSV-associated ARI. RESULTS: Overall, 28&#x202f;689 children younger than 5 years with medically attended ARI were enrolled, including 9536 during September 1, 2023, through April 30, 2024, and 19&#x202f;153 during the same calendar period of 2017-2020. Of these children, 16&#x202f;196 (57%) were male, and 12&#x202f;444 (43.4) were female; the median (IQR) age was 15 (6-29) months. During 2023-2024, the proportion of children with RSV was 23% (2199/9490) among all medically attended episodes, similar to 2017-2020. RSV-associated hospitalization rates in 2023-2024 were similar to average 2017-2020 seasonal rates with 5.0 (95% CI, 4.6-5.3) per 1000 among children younger than 5 years; the highest rates were among children aged 0 to 2 months (26.6; 95% CI, 23.0-30.2). Low maternal RSV vaccine uptake precluded assessment of effectiveness. Overall, 10 of 765 case patients (1%) who were RSV positive and 126 of 851 control patients (15%) who were RSV negative received nirsevimab. Nirsevimab effectiveness was 89% (95% CI, 79%-94%) against medically attended RSV-associated ARI and 93% (95% CI, 82%-97%) against RSV-associated hospitalization. Among 229 sequenced specimens, there were no differences in nirsevimab binding site mutations by infant nirsevimab receipt status. CONCLUSIONS AND RELEVANCE: This analysis documented the continued high burden of medically attended RSV-associated ARI among young children in the US. There is a potential for substantial public health impact with increased and equitable prevention product coverage in future seasons.

Humans

Covid-19 Vaccination During Pregnancy in France: a Descriptive Study of Uptake Using the National Healthcare data System.

Pregnant women and their fetus are at increased risk of complications when infected by SARS-CoV-2. This study describes COVID-19 vaccine uptake during pregnancy in France (i) according to socio-demographic characteristics, and (ii) over calendar time and pregnancy stages. Using the hospital discharge records of the national healthcare database, we identified women ending pregnancy at hospital between Dec 27, 2020, i.e. beginning of Covid-19 vaccine availability, and Dec 31, 2022. Covid-19 vaccinations and SARS-CoV-2 infections were also available on two specific linked databases. Vaccine coverage was defined as uptake of at least one dose of vaccine during the 2-year study period, or more specifically during one of five phases of pregnancy (first, second and third trimesters, pre-conceptional and post-pregnancy periods). We also defined ineligibility as the six-month period following each Covid-19 infection. We calculated weekly rates of vaccination by pregnancy phase, accounting for ineligibility. About 75% of women received at least one dose of vaccine in 2021-2022 vs. 90% in the general population with a similar age structure. About 26% received at least one dose of vaccine while pregnant. The rate was lower among younger women, deprived women, and those living in the south-east of mainland France or in overseas territories. Weekly vaccination rates according to the phase of pregnancy showed that women mostly received vaccination outside the pregnancy trimesters (after or, to a less extent, before pregnancy). Vaccinations during pregnancy mostly occurred in the second trimester. When only elective terminations were considered, weekly rates of vaccination were almost identical, whatever the pregnancy phase (before, during or after pregnancy). Overall, our results show the positive impact of national recommendations on uptake dynamics. Vaccine coverage in pregnant women could be improved with targeted campaigns.

Humans

Dengue and chikungunya vaccines past, present and future: implications for travelers.

PURPOSE OF REVIEW: Novel vaccines for dengue and chikungunya viruses offer new prevention options against two globally important arboviral diseases. This review summarizes recent developments in vaccine licensure, implementation, real-world experience and research priorities, with emphasis on implications for both endemic populations and travelers. RECENT FINDINGS: Of the three live-attenuated dengue vaccines licensed to date, TAK-003 is authorized in >40 countries and Butantan-DV in Brazil, while manufacturing of CYD-TDV is discontinued. Long-term and postmarketing data continue to refine understanding of serotype-specific protection, waning immunity, and rare adverse events.For chikungunya, two single-dose vaccines are licensed-a live-attenuated vaccine (VLA1553) and virus-like particle vaccine (PXVX0317). Uptake is guided by emerging safety and effectiveness data, with each platform offering potential advantages in different settings.Further data on long-term protection, safety, effectiveness, use in vulnerable populations and integration into outbreak management and immunization systems is anticipated. SUMMARY: Dengue and chikungunya vaccines are increasingly being used in immunization programs and pretravel consultations. Further real-world data are needed-particularly for seronegative dengue vaccine recipients and older, immunocompromised or medically at-risk adults. Research priorities include developing single-dose, nonlive dengue vaccines suitable for high-risk groups, understanding long-term chikungunya vaccine performance, and exploring broader flaviviral or pan-arboviral platforms.

Humans

Promoters and Barriers of Vaccine Hesitancy.

This systematic review explores the psychological antecedents of Vaccine Hesitancy, a significant determinant of vaccination behavior. Following PRISMA guidelines, an extensive search was conducted starting from 1673 papers and resulting in 48 publications from various databases. The review identifies psychological factors, specifically cognitive, personality, experiential, and social factors contributing to hesitancy. Cognitive factors include health literacy, conspiracy beliefs, trust, and perceived risk. Personality traits such as extraversion, openness, and psychological capital impact hesitancy, while psychopathy increases it. Personal experiences, like perceived stress and racial discrimination, indirectly affect hesitancy. Social factors, including social relationships and norms, play a significant role in reducing hesitancy. Tailored interventions addressing these factors can enhance vaccine acceptance.

Humans

Possible use of the oxygen uptake rate in the evaluation of BCG vaccines.

Two existing methods suitable for the determination of the oxygen uptake rate (OUR) in BCG suspensions (Warburg and Gilson Oxygraph) are described and compared. With the former method the oxygen uptake rates of the 10 samples of the BCG collaborative assay of the BCG Steering Committee of the International Association of Biological Standardization were determined. When the results are compared with those of colony count and skin reactivity from the collaborative assay, there is a better correlation between OUR and skin reactivity than between OUR and colony count. From the results of our study there is a strong indication that the OUR is a good parameter for quality, and most probably better suited for interlaboratory comparisons than the colony count.

BCG Vaccine

[Rubella infection during pregnancy. Results of serologic diagnosis 1975-1978].

The sera of 663 pregnant women with unknown immune status were tested for HI rubella antibodies between 1975 and 1978 because of exposure to rubella or presence of clinical symptoms. The majority of sera were from women in the first three months of pregnancy. Comparison of the distribution of antibody titers with those in a control group of 670 nonpregnant women of the same age showed no significant difference. The percentage of seronegative subjects was 8.6 in pregnant and 10.5 in nonpregnant women. Eighteen women (2.7%) became infected with rubella virus during pregnancy. Ten of these were devoid of rubella antibodies, representing 17.5% of the seronegatives. Diagnosis was confirmed by seroconversion and rise in antibody titer. The remaining 8 women had antibodies in the first blood specimen. Diagnosis was established by a fourfold or greater increase in titer or by the demonstration of rubella specific IgM-antibodies in a single specimen. It is of interest that almost all the pregnant women with rubella infection had clinical symptoms such as fever or exanthem. The results of this study show that the aim of complete rubella prophylaxis in women of childbearing age has not yet been achieved. It is therefore necessary to increase the uptake of rubella vaccine by schoolgirls and reduce the percentage of seronegative adult women by single vaccination and vaccination in the postpartum period.

Adolescent

A Multimethod Evaluation to Assess Feasibility, Acceptability, and Preliminary Efficacy of HPVVaxFacts, a Tailored Mobile Web App, for Parents With Unvaccinated Children: Pilot 2-Arm Randomized Controlled Trial.

BACKGROUND: Mobile health (mHealth) interventions may improve provider-parent communication on human papillomavirus (HPV) vaccination to reduce concerns, and increase intention and uptake. HPVVaxFacts (233 Analytics) is a novel, mobile web app delivering tailored education based on the Health Belief Model and Theory of Reasoned Action, addressing parental concerns preclinic visit. OBJECTIVE: This study aimed to assess the feasibility, acceptability, and preliminary efficacy of HPVVaxFacts among parents of adolescents aged 9-17 years. METHODS: We conducted a pilot, randomized controlled trial in 2 urban Tennessee clinics from June to September 2023 comparing 2 groups: tailored education via HPVVaxFacts mobile web app (intervention, n=27), and nutrition education (attention control, n=30). Eligible parents had or were caregivers to a child aged 9 to 17 years unvaccinated against HPV, had a mobile phone, had an upcoming clinic visit, and spoke English. The recruitment strategy was patient intake software-Phreesia (Phreesia, Inc) and eClinicalWorks (eClinicalWorks). Although unblinded, parents could deduce their study arm assignment. Providers were blinded. Feasibility, acceptability, and preliminary efficacy (HPV vaccine knowledge, concerns, intentions, and vaccination rates) were assessed using multimethod evaluation. Parents were assessed at baseline and immediately post intervention via surveys. Vaccination rates were assessed at 12 months post intervention via electronic health records. Nineteen parent interviews were conducted up to 9 months post intervention. A clinic staff consultation (n=6) was 1 month post intervention. RESULTS: Of 57 enrolled parents, most were female (52/57, 91%), non-Hispanic White (44/57, 77%), had &#x2264;US $80,000 household income (32/57, 56%), and had some college or less (27/57, 47%). In total, 81% (29/36) of parents viewed HPVVaxFacts. Post intervention, HPV vaccine initiation was higher in the intervention group compared to the attention control group (48% vs 17%; difference 0.24; 95% CI 0.03-0.46; P=.01). Parents in the HPVVaxFacts arm demonstrated a greater reduction in knowledge (ie, knowledge increase; mean change: -0.6 vs 0.1) and concern scores (mean change: -3.4 vs -1.4) than those in the nutrition education arm. However, between-arm differences were not statistically significant (P=.13 and P=.14, respectively). The majority found the study protocol and HPVVaxFacts acceptable. Benefits of HPVVaxFacts include confirming their decision to vaccinate, supporting parent-child discussion on the vaccine, and answering questions preclinic visit or offering questions for the provider. Study protocol delivery and mobile web app instructions were suggested areas for improvement. Barriers for HPVVaxFacts use include content in English only and digital format. CONCLUSIONS: Our study suggests HPVVaxFacts was feasible and acceptable among parents to provide previsit, tailored information on HPV vaccination. Outcomes offer a positive trajectory but need more exploration. Next steps include a well-powered efficacy trial to determine the impact of HPVVaxFacts on initiation vaccine rates and parental hesitancy factors, as well as to explore an interaction, effect modification, and mediation among different variables.

Humans

Uptake of maternal antibody by the neonatal pig following intramuscular and intramammary vaccination of the preparturient sow.

Administration of heat inactivated Escherichia coli antigens by intramuscular and intramammary routes induced elevated antibody levels in sow serum and colostrum, predominantly associated with IgG. Colostral IgG accounted for approximately 80 per cent of the total antibody activity, and there was a similar distribution in the sera of one-day-old piglets. The additional antibody activity was carried almost entirely by IgM following intramuscular injections and was evenly distributed between IgM and IgA following intramammary stimulation. The distribution of antibody activity and all three major immunoglobulin classes in colostrum and milk from individual mammary glands was remarkably uniform. A similar uniformity was inferred for the ingestion and absorption of colostrum by individual piglets as judged by the contents of their blood sera during the neonatal period.

Animals

Induced metabolic sequelae of tularemia in the rat: correlation with tissue damage.

Serum and liver zinc concentration, amino acid uptake by liver, seromucoid content, and alpha2-macrofetoprotein production were measured in vaccinated as well as nonimmune rats exposed to either virulent (SCHU S4) or attenuated (LVS) strains of Francisella tularensi. It appears that liver damage (pyogranulomatous lesions) must occur before there is any alteration in the above variables. The presence of bacteria in the liver is not of itself sufficient to lead to the onset of systemic, induced metabolic sequelae (IMS). The occurrence of zinc redistribution in all instances of increased serum protein synthesis may imply a necessary relationship between these two sequelae. Amino acid redistribution does not appear to be linked to serum protein synthesis. An endogenous mediator of systemic IMS can be detected in tularemic rats by injection of the serum of these animals into healthy recipients. The occurrence of zinc redistribution and increased serum protein synthesis in some groups of rats in the absence of amino acids uptake by liver, as well as the apparent differential dose responsiveness of these responses, are suggestive of a multiplicity of endogenous mediators.

Amino Acids

From Infection Control to Healthcare System Resilience: Lessons Learned from SARS-CoV-2 Research in Healthcare Workers.

The COVID-19 pandemic placed unprecedented pressure on healthcare systems and exposed healthcare workers (HCWs) to biological hazards, organizational pressures, and psychological strain. Evidence generated during the emergency shows that HCW protection cannot rely on isolated measures, but requires an integrated framework combining epidemiological surveillance, contact tracing, infection prevention and control, vaccination, occupational health, and workforce support. Contact tracing helped identify occupational exposures and clarify how duration, proximity, and inadequate use of personal protective equipment jointly shaped infection risk. Subsequent studies of reinfection showed that susceptibility reflected the interaction of viral circulation, individual immunity, and vaccination status. Vaccination reduced the clinical impact of SARS-CoV-2 and supported service continuity, although uptake depended on trust, communication, and management of adverse event concerns. The pandemic also highlighted substantial economic consequences and a high burden of psychological distress and burnout among HCWs. Building on this evidence, future preparedness should translate these lessons into permanent, adaptable infrastructure rather than temporary emergency arrangements, integrating interoperable, AI-assisted surveillance capable of combining occupational, diagnostic, vaccination, and genomic data to detect emerging risks early, while ensuring robust data governance and human oversight. Equally central is the need to address long-term workforce vulnerabilities, including Long COVID, attrition, and burnout, through early identification, rehabilitation, flexible return-to-work models, and sustained psychosocial support. Achieving this requires structured multidisciplinary collaboration among occupational medicine, infection control, epidemiology, mental health, and digital health specialists, moving from fragmented infection-control protocols to an integrated, proactive, and learning-oriented preparedness strategy. Protecting HCWs is therefore not only an occupational safety priority but a foundational prerequisite for safe, equitable, and sustainable healthcare delivery during future infectious threats.

Humans

Effect of immunization on the cyclic AMP level and 3H-thymidine incorporation in cultured lymphoid cells.

The cyclic AMP level and the uptake of 3H-thymidine were studied in short-term suspension cultures of guinea pig lymphoid cells. Spleen cells from animals immunized 3 days previously with typhoid vaccine were shown to differ in three respects from the normal cells: (1) The level of cyclic AMP was higher. (2) The cyclic AMP increase following addition of isoproterenol or adenosine was abolished. (3) Isoproterenol (10(-5) to 10(-4) M) stimulated the uptake of 3H-thymidine in cells from immunized animals, while the uptake into normal cells was inhibited by these concentrations. A higher dose of isoproterenol (10(-3) M) inhibited 3H-thymidine uptake in both immunized and normal cells. The results reveal certain biochemical alterations in splenic lymphocytes after immunization. An altered 3H-thymidine uptake may be caused by the modified cyclic AMP metabolism in cells from immunized animals.

Adenosine

Macrophage fusion factor elicited from BGG-sensitized lymphocytes.

Lymphocytes obtained from rabbit lymph nodes sensitized to bovine gamma globulin produce in vitro the lymphokine macrophage fusion factor (MFF) which mediates the fusion of approximately 100% of normal alveolar and oil-induced peritoneal macrophages. Giant cells (GC) of Langhans and foreign body type form large syncytia containing as many as several hundred nuclei per cell. Nuclei of GC appear more spherical and larger than those of the normal mononucleated macrophages, and they possess several prominent nucleoli. Giant cells of peritoneal macrophage origin show enhanced intracytoplasmic vacuolization. Normal macrophages cultured as a monolayer in MFF-rich supernatants form cell clusters which progressively fuse during the 24-hour incubation period. A signoid dose-response curve was obtained for cell fusion with MFF-rich supernatants possessing high titers, ie, the latter supernatants undiluted partially inhibited macrophage fusion. MIF-like activity was detected in MFF-rich supernatants as well as a factor(s) which inhibited 3H-thymidine uptake by giant cells.

Animals

Engineered Bacteriophages in Cancer Immunotherapy: Emerging Concepts and Potential Integration with CAR-T Cell Therapy.

Due to antigen heterogeneity, restricted immune cell trafficking and an immunosuppressive, nutrient-restricted tumour microenvironment, solid tumours remain resistant to modern immunotherapies. Engineered bacteriophages offer a modular framework to overcome these obstacles: programmable virus-like particles with scalable production. Through genome engineering, capsid decoration with mammalian cell-targeting ligands, or hybrid AAV/phage systems, engineered bacteriophages can display tumour-associated antigens, enhance receptor-mediated uptake and deliver therapeutic payloads such as cytokines, chemokines and suicide genes without naturally infecting mammalian cells. These features support their use as vaccine platforms, immunological adjuvants and targeted gene-delivery vehicles. These may enable more precise, tumour-localized therapeutic intervention. Phages can engage innate immune pathways, including TLR9, TLR3/7/8, cGAS-STING and AIM2, promoting dendritic cell maturation and inflammatory mediators that may convert immunologically "cold" tumours into inflamed microenvironments. Their multivalent antigen display enhances B- and T-cell priming, while cDC1-mediated cross-presentation supports cytotoxic CD8+ T-cell responses and immunological memory. In CAR-T therapy, engineered phages may improve tumour homing through chemokine modulation, support persistence through local cytokine delivery, reduce antigen escape by presenting multiple tumour epitopes, and limit T-cell exhaustion through dominant-negative receptor strategies or local checkpoint blockade. This review summarizes engineering approaches, delivery systems, manufacturing, biodistribution, dosing, and safety issues, including immunogenicity, pre-existing anti-phage antibodies and horizontal gene transfer. It also distinguishes therapeutic engineered phage particles from phage display technologies used for molecular discovery. Despite encouraging results integrating modified bacteriophages with CAR-T cell therapy, the evidence remains mostly preclinical, indicating both substantial translational prospects and crucial obstacles for future clinical development.

CAR-T cell therapy