Vaccine Efficacy Research Articles

Navigating parental attitudes on childhood vaccination in Jordan: a cross-sectional study

ABSTRACT This study investigated parental attitudes toward childhood vaccination in Jordan, focusing on acceptance, concerns, and perceptions. A cross-sectional survey conducted from January to February 2024 included 939 parents. Findings indicated that 85.4% (n = 802) of respondents received the COVID-19 vaccine, while only 25% (n = 229) vaccinated their children. Concerns regarding vaccine safety and efficacy were prevalent, with 63.9% (n = 600) expressing worries about side effects and 46.9% (n = 440) trusting immunization programs. Post-pandemic, 34% (n = 319) reported a more negative attitude. Logistic regression showed parents not vaccinating their children against COVID-19 were significantly less likely to exhibit positive attitudes toward childhood vaccination (OR = 0.412, p < 0.001). Older participants were more inclined toward negativity post-pandemic (OR = 1.031, p = 0.007). In conclusion, parental attitudes shifted post-COVID-19, reflecting hesitancy and decreased trust. Addressing concerns and restoring confidence are crucial, especially for children’s health. Education through healthcare providers and dispelling social media misinformation are essential. Implementing strategies to enhance post-pandemic vaccine acceptance is imperative for preventing outbreaks of vaccine-preventable diseases.

Efficacy of Genotype-matched Vaccine Against Re-emerging Genotype V Japanese Encephalitis Virus

Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV), is a highly threatening disease with no specific treatment. Fortunately, the development of vaccines has enabled effective defense against JE. However, re-emerging genotype V (GV) JEV poses a challenge as current vaccines are genotype III (GIII)-based and provide suboptimal protection. Given the isolation of GV JEVs from Malaysia, China, and the Republic of Korea, there is a concern about the potential for a broader outbreak. Under the hypothesis that a GV-based vaccine is necessary for effective defense against GV JEV, we developed a pentameric recombinant antigen using cholera toxin B as a scaffold and mucosal adjuvant, which was conjugated with the E protein domain III of GV by genetic fusion. This GV-based vaccine antigen induced a more effective immune response in mice against GV JEV isolates compared to GIII-based antigen and efficiently protected animals from lethal challenges. Furthermore, a bivalent vaccine approach, inoculating simultaneously with GIII- and GV-based antigens, showed protective efficacy against both GIII and GV JEVs. This strategy presents a promising avenue for comprehensive protection in regions facing the threat of diverse JEV genotypes, including both prevalent GIII and GI as well as emerging GV strains.

Pulmonology: What You May Have Missed in 2023.

The field of pulmonology saw significant advances in 2023. The publications highlighted in this article address advances and changes in practice related to asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, pleural disorders, and sleep-disordered breathing. One article reviews data examining the efficacy of vaccination against respiratory syncytial virus, a respiratory viral illness that has had devastating effects globally. Four studies evaluate the role of various therapies in COPD, including dupilumab, ensifentrine, pulmonary rehabilitation programs, and lung volume reduction versus endobronchial valves. Another study explores the effect on vascular events of positive-pressure ventilation in patients with sleep-disordered breathing and recent stroke. The use of combination therapy with rituximab and mycophenolate mofetil on progression-free survival in patients with nonspecific interstitial pneumonia is the topic of another study. We also highlight an update of clinical recommendations for the evaluation of patients with pleural disorders and a systematic review analyzing the effectiveness of inhaled corticosteroids as a supplement to dual therapy for COPD.

A TriAdj-Adjuvanted Chlamydia trachomatis CPAF Protein Vaccine Is Highly Immunogenic in Pigs

Chlamydia trachomatis (Ct) infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs, as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we used the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial-protease-like activity factor (CPAF) protein. We tested two weekly administration options—twice intranasal (IN) followed by twice intramuscular (IM) and twice IM followed by twice IN. We assessed the humoral immune response in both serum using CPAF-specific IgG (including antibody avidity determination) and also in cervical and rectal swabs using CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed following in vitro CPAF restimulation via IFN-γ and IL-17 ELISpots, as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity, as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response. Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response with CD4 T cells. In IM/IN-vaccinated pigs, these cells also significantly downregulated their CCR7 expression, a sign of differentiation into peripheral-tissue-homing effector/memory cells. Conclusively, this study demonstrates the strong immunogenicity of the IM/IN-administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test the vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates the suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

Periodontal vaccines via plantibodies: Bridging the gap between aspiration and achievement

Periodontitis, a multifaceted immune-inflammatory disorder, is intricately linked to systemic conditions such as cardiovascular disease and diabetes mellitus. Recent advancements in cellular and molecular biology have catalyzed the development of innovative vaccination strategies for various viral diseases. The concept of vaccination, pioneered by Edward Jenner in the late 18th century, capitalizes on the phenomenon of acquired immunity following recovery from an illness. Jenner's groundbreaking work with cowpox virus, which conferred cross-protection against smallpox, laid the foundation for modern vaccination practices.The advent of microbial genome sequencing and bioinformatics has revolutionized our ability to explore the genetic makeup of human pathogens comprehensively. This approach holds promise for identifying novel targets for antimicrobial drugs and vaccines, providing new avenues for combating infectious diseases.Given the pervasive nature of periodontal disease, there is an imperative need for effective management and prevention strategies. In the realm of immunization, the emergence of plant-based vaccines represents a novel paradigm. This review employed various search engines, including PubMed, Embase, Web of Science, Cochrane, Medline, and Google Scholar, to identify pertinent articles in medical and dental research. The findings from these studies underscore the potential efficacy of plant-derived vaccines in addressing a diverse range of disorders, including periodontal disease.This comprehensive review sheds light on the broad spectrum of applications of plant-based vaccines in periodontal care. By harnessing the unique properties of plant-derived antigens, these vaccines hold promise for offering safe, effective, and scalable solutions for the prevention and management of periodontitis. Further research and clinical trials are warranted to explore the full potential of plant-based vaccines in revolutionizing periodontal therapeutics.

The Effect of an Attenuated Live Vaccine against Salmonid Rickettsial Septicemia in Atlantic Salmon (Salmo salar) Is Highly Dependent on Water Temperature during Immunization

Salmonid Rickettsial Septicemia (SRS), caused by the bacterium Piscirickettsia salmonis, is the main reason for antibiotic usage in the Chilean aquaculture industry. In 2016, a live attenuated vaccine (ALPHA JECT LiVac® SRS, PHARMAQ AS) was licensed in Chile and has been widely used in farmed salmonids since then. In experimental injection and cohabitation laboratory challenge models, we found that the vaccine is effective in protecting Atlantic salmon (Salmo salar) for at least 15 months against P. salmonis-induced mortality. However, the protection offered by the vaccine is sensitive to temperature during immunization. Fish vaccinated and immunized at 10 °C and above were well protected, but those immunized at 7 °C and 8 °C (the lower end of the temperature range commonly found in Chile) experienced a significant loss of protection. This temperature-dependent loss of effect correlated with the amount of vaccine-strain RNA detected in the liver the first week after vaccination and with in vitro growth curves, which failed to detect any growth at 8 °C. We found that good vaccine efficacy can be restored by exposing fish to 15 °C for the first five days after vaccination before lowering the temperature to 7 °C for the remaining immunization period. This suggests that maintaining the correct temperature during the first few days after vaccination is crucial for achieving a protective immune response with ALPHA JECT LiVac® SRS. Our results emphasize the importance of temperature control when vaccinating poikilothermic animals with live vaccines.

Using social media surveys and interventions to address vaccine hesitancy in Saudi Arabia

Background: Countering COVID-19 vaccine hesitancy has been a challenge in Saudi Arabia, one of the countries affected most by the pandemic in the Eastern Mediterranean Region. Aims: To identify information needs, perceived benefits, concerns, trusted information sources, social norms, and predictors for COVID-19 vaccine uptake in Saudi Arabia and identify effective messaging strategies to increase vaccination intentions among the unvaccinated. Method: Between March and April 2021, we conducted an online cross-sectional survey (N = 2883), and in part, a randomized experiment for unvaccinated participants (n = 675) in Saudi Arabia using Facebook Ads and Messenger. Unvaccinated participants were randomly assigned to 1 of 5 message conditions and after message exposure, participants were asked if they planned to take the COVID-19 vaccine. Results: In total, 2883 adults participated in the survey. All message framings worked equally well, with no statistically significant difference between the arms. Approximately 80% of the participants across all message conditions said they intended to vaccinate. However, participants wanted to know more about the vaccines; about 35% wanted to know more about vaccine efficacy, 31.5% about safety, 26.8% about health authority’s recommendation, and 3.7% about where to get the vaccines. Health workers (61.4%) and scientists and epidemiologists (25.7%) were the most trusted sources. Others were family members (7.5%), community leaders (2.2%), religious leaders (1.6%), friends (1.4%), and celebrities and social media influencers (0.2%). Conclusion: Vaccine hesitancy can be overcome by understanding individuals’ decision-making processes and using effective risk communication targeted to their needs.

The Prevalence and Determinants of Hesitancy for Regular COVID-19 Vaccination among Primary Healthcare Patients with Asthma or COPD in Greece: A Cross-Sectional Study

The emergence of novel coronavirus mutations and signs of the waning immunity provided by COVID-19 vaccines underscore the importance of regular vaccination. This study aimed to investigate the prevalence of regular COVID-19 vaccination hesitancy and the factors that influence it among patients with asthma or chronic obstructive pulmonary disease (COPD) who visited primary care centers. The cross-sectional study was conducted in six primary healthcare centers in Crete, Greece (October–December 2023). Participants completed a questionnaire, which included questions about socio-demographic characteristics, health status, previous COVID-19 booster vaccination, attitudes, and beliefs about COVID-19 vaccination. Multivariate logistic regression was used to identify the factors that influenced vaccine hesitancy. Of the 264 participants, 65% exhibited hesitancy towards COVID-19 booster vaccination. Female gender, middle age, lower educational attainment, depression diagnosis, concerns about vaccine side effects, lack of confidence in vaccine efficacy, and reliance on media information were positively associated to vaccine hesitancy. Conversely, those having a cardiovascular disease or type 2 diabetes, those generally adhering to the recommendations of the treating physician, and those having previously received the flu vaccine or more than three COVID-19 vaccine doses were positively associated with regular COVID-19 vaccinations. Consequently, our findings could help develop strategies that could potentially reduce regular vaccination hesitancy among patients with asthma or COPD.

Career decisions in artistic professions during the COVID-19 pandemic in Germany—an experimental study

The COVID-19 pandemic has had a significant impact on the professional situation in artistic professions. Repeated lockdowns resulted in the cancellation of cultural events and exacerbated economic challenges, depriving artists and people working in the culture industry of their primary source of income. Such drastic conditions could lead to important professional decisions, including career changes. This study aimed to determine the factors that could influence career decisions among artistic professionals during a second pandemic lockdown period in Germany. To examine whether health concerns or financial struggles are more important in shaping artistic professionals’ decisions to change or stay in their profession, a vignette experiment was conducted in an online survey (n = 788) in the winter of 2020–2021. In the experiment’s 2*3-factorial randomised design, all respondents were asked to put themselves in the role of artists and make decisions about career changes under different income conditions or with different health prospects. The vignette experiment revealed that income losses related to career changes decreased the willingness to change careers, whereas health prospects (hypothetical differences in vaccine efficacy) did not affect the decisions. In addition, other variables were found to explain career decisions; female gender and signs of a depressive disorder were associated with greater willingness for career turnover, whereas a higher educational level and status of earning one’s livelihood in the culture industry were associated with a diminished tendency for career turnover. The latter impact factor was interpreted as a kind of “don´t give up effect” that is particularly observable among artistic professionals.

HPV Vaccine Issues in Japan: A review of our attempts to promote the HPV vaccine and to provide effective evaluation of the problem through social-medical and behavioral-economic perspectives

In Japan, subsidies from local and national government programs for HPV vaccination of girls aged 13–16 began in 2010. By 2013, HPV vaccines were being used routinely for vaccinating girls aged 12–16 as part of its national immunization program. However, in June of 2013, in response to reports of possible adverse reactions to the vaccine, Japan’s Ministry of Health, Labor, and Welfare (MHLW) announced a ‘temporary suspension’ of its governmental recommendation for HPV vaccination. The vaccination rate quickly dropped from 70 % of age-eligible girls to almost zero. It was not until 2021 that the government’s recommendation suspension finally ended. The efficacy and safety of the HPV vaccine is now well documented, yet Japan has failed to reestablish any credible level of HPV vaccination. The World Health Organization (WHO) warned that Japan’s HPV vaccination debacle was likely to result in real harm to the girls who lacked its protection; something we have already demonstrated with real-world data. To reinvigorate the HPV vaccination program in Japan to its prior levels, in the face of the current high level of HPV vaccine hesitancy, we will have to address the irrationality of human decision-making pointed out by behavioral economics. The Japanese government must act expeditiously to promote stronger cervical cancer control measures.

Social, Ethical and Regulatory implications of conducting a malaria Vaccine Efficacy trial in a human infection study in Kenya (SERVE-Kenya): A study protocol

Malaria remains an important public health problem in many LMICs, including Kenya – necessitating alternative prevention and control strategies. Malaria human infection studies (HIS) – trials that involve the deliberate infection of healthy volunteers with malaria parasites to assess the efficacy of potential vaccine and drug candidates and to understand the innate and acquired protection against malaria parasites - have become an important approach to fast-track the development of a malaria vaccine. The KEMRI-Wellcome Trust Research Programme (KWTRP) otherwise known as the KEMRI Centre for Geographic Medicine Research (Coast) (KEMRI CGMRC) has developed expertise in setting up and running research on malaria HIS, with two completed and two planned in the coming months. One of the planned studies is an EDCTP-funded Phase IIb malaria vaccine efficacy trial within a HIS. While all scientific proposals at KWTRP are carefully reviewed by national and international science and ethics review bodies and are supported by a well-developed local community engagement platform, research to understand the social, ethical and regulatory issues for HIS from a grounded perspective is in early stages of development, especially in LMICs. Given the particular opportunities provided by the KWTRP’s experience in running HIS, expertise in embedded social science research and the presence of a well-established community engagement platform, we plan to conduct a social science study within the HIS-based Phase IIb malaria vaccine trial. The overall aim is to contribute to the development of locally responsive policies on the ethical conduct of malaria vaccine efficacy studies involving the use of a HIS in Kenya. Data will be collected from a range of HIS stakeholders, including HIS participants, community members, HIS research team, ethics committees, regulatory authorities and policy makers through surveys, interviews, group discussions, participatory workshops, observations and document review. This is an EDCTP-funded Career Development Fellowship project awarded to PCC.

The role of cGAMP via the STING pathway in modulating germinal center responses and CD4 T cell differentiation

Germinal center (GC) responses are essential for establishing protective, long-lasting immunity through the differentiation of GC B cells (BGC) and plasma cells (BPC), along with the generation of antigen-specific antibodies. Among the various pathways influencing immune responses, the STING (Stimulator of Interferon Genes) pathway has emerged as significant, especially in innate immunity, and extends its influence to adaptive responses. In this study, we examined how the STING ligand cGAMP can modulate these key elements of the adaptive immune response, particularly in enhancing GC reactions and the differentiation of BGC, BPC, and follicular helper T cells (TFH). Employing in vivo models, we evaluated various antigens and the administration of cGAMP in Alum adjuvant, investigating the differentiation of BGC, BPC, and TFH cells, along with the production of antigen-specific antibodies. cGAMP enhances the differentiation of BGC and BPC, leading to increased antigen-specific antibody production. This effect is shown to be type I Interferon-dependent, with a substantial reduction in BPC frequency upon interferon (IFN)-β blockade. Additionally, cGAMP’s influence on TFH differentiation varies over time, which may be critical for refining vaccine strategies. The findings elucidate a complex, antigen-specific influence of cGAMP on T and B cell responses, providing insights that could optimize vaccine efficacy.

Updated Public Health Impact and Cost Effectiveness of Recombinant Zoster Vaccine in Canadian Adults Aged 50 Years and Older.

The aim of this study was to update previously estimated public health impact and cost effectiveness of recombinant zoster vaccine (RZV) for the prevention of herpes zoster (HZ) in Canadians aged ≥50 years using longer-term RZV efficacy and waning data and real-world coverage and completion. A multicohort Markov model was used to conduct a cost-utility analysis comparing RZV with no HZ vaccination among Canadians aged ≥50 years. Real-world data were used for first-dose coverage (17.5%) and second-dose completion (65%). Vaccine efficacy and waning data were applied from up to 8-year follow-up from the ZOE-50 and ZOE-70 clinical trials. Incremental costs and benefits were calculated using a lifetime horizon from the healthcare payer (base case) and societal perspectives. A discount rate of 1.5% was applied to costs and quality-adjusted life-years (QALYs). The model estimated that RZV would prevent 303,835 HZ cases, 83,256 post-herpetic neuralgia (PHN) cases, 39,653 other complications, and 99 HZ-related deaths compared with no HZ vaccination. Incremental cost-effectiveness ratios (ICERs) were estimated to be $27,486 and $22,097 per QALY (2022 Canadian dollars [CAN$]) from the healthcare payer and societal perspectives, respectively. The base-case ICER was most sensitive to a lower percentage of initial HZ cases with PHN. Almost all probabilistic sensitivity analysis simulations (98.1%) resulted in ICERs <CAN$50,000 per QALY. RZV is expected to remain a cost-effective option for Canadian adults aged ≥50 years when using longer-term RZV efficacy and waning estimates, although the estimated public health impact was smaller than in the previous analysis (due to lower coverage/completion estimates).

Vaccine Efficacy, Impact, Hesitancy, and Acceptance: Trends for Public Health

Vaccines are indispensable tools in the battle against infectious diseases and hold great potential in combating a myriad of other diseases [...]

CoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits

One of the strategies towards an effective HIV-1 vaccine is to elicit broadly neutralizing antibody responses that target the high HIV-1 Env diversity. Here, we present an HIV-1 vaccine candidate that consists of cobalt porphyrin-phospholipid (CoPoP) liposomes decorated with repaired and stabilized clade C HIV-1 Env trimers in a prefusion conformation. These particles exhibit high HIV-1 Env trimer decoration, serum stability and bind broadly neutralizing antibodies. Three sequential immunizations of female rabbits with CoPoP liposomes displaying a different clade C HIV-1 gp140 trimer at each dosing generate high HIV-1 Env-specific antibody responses. Additionally, serum neutralization is detectable against 18 of 20 multiclade tier 2 HIV-1 strains. Furthermore, the peak antibody titers induced by CoPoP liposomes can be recalled by subsequent heterologous immunization with Ad26-encoded membrane-bound stabilized Env antigens. Hence, a CoPoP liposome-based HIV-1 vaccine that can generate cross-clade neutralizing antibody immunity could potentially be a component of an efficacious HIV-1 vaccine.

Establishment of an intragastric surgical model using C57BL/6 mice to study the vaccine efficacy of OMV-based immunogens against Helicobacter pylori.

Chronic gastritis is one of the major symptoms of gastro-duodenal disorders typically induced by Helicobacter pylori (H. pylori). To date, no suitable model is available to study pathophysiology and therapeutic measures accurately. Here, we have presented a successful surgical infection model of H. pylori-induced gastritis in C57BL/6 mice that resembles features similar to human infection. The proposed model does not require any preparatory treatment other than surgical intervention. C57BL/6 mice were injected with wild-type SS1 (Sydney strain 1, reference strain) directly into the stomach. Seven days post infection, infected animals showed alterations in cytokine responses along with inflammatory cell infiltration in the lamina propria, depicting a prominent inflammatory response due to infection. To understand the immunogenicity and protective efficacy, the mice were immunized with outer membrane vesicles (OMVs) isolated from an indigenous strain with putative virulence factors of H. pylori [A61C (1), cag+/vacA s1m1]. In contrast to the non-immunized cohort, the OMV-immunized cohort showed a gradual increase in serum immunoglobulin(s) levels on the 35th day after the first immunization. This conferred protective immunity against subsequent challenge with the reference strain (SS1). Direct inoculation of H. pylori into the stomach influenced infection in a short time and, more importantly, in a dose-dependent manner, indicating the usefulness of the developed model for pathophysiology, therapeutic and prophylactic studies.

Development of a dual immunochromatographic test strip to detect E2 and Erns antibodies against classical swine fever

BackgroundIt is essential to consider a practical antibody test to successfully implement marker vaccines and validate vaccination efficacy against classical swine fever virus (CSFV). The test should include a serological antibody assay, combined with a tool for differentiating infected from vaccinated animals (DIVA). The immunochromatographic test strip (ICS) has been exclusively designed for detecting CSFV E2 antibodies while lacking in detecting Erns antibodies, which can be employed and satisfy DIVA strategy. This study developed a novel ICS for detecting CSFV E2/Erns dual-antibody. The effectiveness of ICS in evaluating the DIVA capability of two novel chimeric pestivirus vaccine candidates was assessed.MethodsRecombinant E2 or Erns protein was transiently expressed in the plant benthamiana using Agrobacterium tumefaciens. ICS was subsequently assembled, and goat anti-rabbit IgG and recombinant CSFV E2 or Erns protein were plated onto the nitrocellulose membrane as control and test lines, respectively. The sensitivity and specificity of ICS were evaluated using sera with different neutralizing antibody titers or positive for antibodies against CSFV and other pestiviruses. The coincidence rates for detecting E2 and Erns antibodies between ICS and commercial enzyme-linked immunosorbent assay (ELISA) kits were also computed. ICS performance for DIVA capability was evaluated using sera from pigs vaccinated with conventional vaccine or chimeric vaccine candidates.ResultsE2 and Erns proteins were successfully expressed in N. benthamiana-produced recombinant proteins. ICS demonstrated high sensitivity in identifying CSFV E2 and Erns antibodies, even at the low neutralizing antibody titers. No cross-reactivity with antibodies from other pestiviruses was confirmed using ICS. There were high agreement rates of 93.0 and 96.5% between ICS and two commercial ELISA kits for E2 antibody testing. ICS also achieved strong coincidence rates of 92.9 and 89.3% with two ELISA kits for Erns antibody detection. ICS confirmed the absence of CSFV Erns-specific antibodies in sera from pigs vaccinated with chimeric vaccine candidates.ConclusionE2 and Erns proteins derived from the plant showed great potential and can be used to engineer a CSFV E2/Erns dual-antibody ICS. The ICS was also highly sensitive and specific for detecting CSFV E2 and Erns antibodies. Significantly, ICS can fulfill the DIVA concept by incorporating chimeric vaccine candidates.

COVID-19 vaccine efficacy in participants with weakened immune systems from four randomized-controlled trials.

Although the SARS-CoV-2 vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions. A post-hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, COVID-19 vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS (NTIS) individuals starting at 14 days after completion of the primary series through the blinded phase for each of the four trials. An analysis of participants living with well-controlled HIV was conducted using the same methods. 3,852/30,351 (12.7%) Moderna participants, 3,088/29,868 (10.3%) Novavax participants, 3,549/32,380 (11.0%) AstraZeneca participants, and 5,047/43,788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (versus placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants vs NTIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with HIV. For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared to those with non-tempered immune systems in the four COVID-19 vaccine randomized controlled efficacy trials.

Trivalent and quadrivalent seasonal influenza vaccine in adults aged 60 and older: a systematic review and network meta-analysis

ObjectivesTo compare the efficacy of influenza vaccines of any valency for adults 60 years and older.Design and settingSystematic review with network meta-analysis (NMA) of randomised controlled trials (RCTs). MEDLINE, EMBASE,...

Targeting PCSK9 to upregulate MHC-II on the surface of tumor cells in tumor immunotherapy.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), the last member of the proprotein convertase family, functions as a classic regulator of low-density lipoprotein (LDL) by interacting with low-density lipoprotein receptor (LDLR). Recent studies have shown that PCSK9 can affect the occurrence and development of tumors and can be used as a novel therapeutic target. However, a comprehensive pan-cancer analysis of PCSK9 has yet to be conducted. The potential oncogenic effects of PCSK9 in 33 types of tumors were explored based on the datasets of The Cancer Genome Atlas (TCGA) dataset. In addition, the immune regulatory role of PCSK9 inhibition was evaluated via in vitro cell coculture and the tumor-bearing mouse model. Finally, the antitumor efficacy of targeted PCSK9 combined with OVA-II vaccines was verified. Our results indicated that PCSK9 was highly expressed in most tumor types and was significantly correlated with late disease stage and poor prognosis. Additionally, PCSK9 may regulate the tumor immune matrix score, immune cell infiltration, immune checkpoint expression, and major histocompatibility complex expression. Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Combining PCSK9 inhibitors could enhance the efficacies of OVA-II tumor vaccine monotherapy. Conclusively, our pan-cancer analysis provided a more comprehensive understanding of the oncogenic and immunoregulatory roles of PCSK9 and demonstrated that targeting PCSK9 could increase the efficacy of long peptide vaccines by upregulating DC infiltration and MHC-II expression on the surface of tumor cells. This study reveals the critical oncogenic and immunoregulatory roles of PCSK9 in various tumors and shows the promise of PCSK9 as a potent immunotherapy target.