Evaluation of the Effect of HSV-tk/GCV Adenoviral Vector Vaccine Candidate in Inhibiting the Growth of Myeloma Tumors by Inducing Autophagy in BALB/c Mice

mRNA and adenoviral vector vaccine platforms were used for the primary series of COVID-19 vaccines in many countries. However, the distinct immunogenic properties on these platforms remain less understood. We traced neutralizing antibodies, memory B cells, and T cells longitudinally in cohorts that received either mRNA (BNT162b2 or mRNA-1273) or adenoviral vector (ChAdOx1) vaccines with homologous or heterologous regimens (total 9 groups, n = 26–28 for each group) at 4 weeks interval. The priming and boosting effects on various immune parameters were comparably assessed between mRNA and adenoviral vector platforms. We found that initial priming by adenoviral vector vaccine elicited robust T cell responses, but B cell responses, including antibody titers, were relatively lower than those elicited by mRNA priming. The dissociation between T cell and antibody responses were exaggerated at greater extents after the homologous booster with the adenoviral vector vaccine, resulting in 5-19-fold lower antibody titers despite comparable spike-specific T cell numbers at day 28 after the boost. Robust IFN-γ and few IL-2 and IL-5 production characterized T cell functionality primed by adenoviral vector. Boosting with mRNA vaccines restored their IL-2 and IL-5 production at some extents, but the IL-5 T cell responses elicited by adenoviral vector/mRNA heterologous regimen waned faster than those by mRNA homologous regimen. Thus, our data revealed that the cytokine production of helper T cells was skewed by adenoviral vector priming, leading to the attenuated IL-2 and IL-5 responses which were prolonged even after mRNA boosting, suggesting an imprinting of T-cell functionality depending on the vaccine platform used for initial priming. These results highlight the importance of selecting vaccine platforms based on the immunogenic properties.

Functional analyses of vitt patient-derived PF4-antibodies and adenoviral vaccine compounds reveal unique patient-specific profiles of multicellular activation

Vaccination Strategies for Patients with B-CLL.

ABSTRACTIntroduction: Despite their appeal as vaccine vectors, adenoviral vectors are yet unable to induce protective immune responses against some weakly immunogenic antigens. Additionally, the maximum doses of adenovirus-based vaccines are limited by vector-induced toxicity, causing vector elimination and diminished immune responses against the target antigen. In order to increase immune responses to the transgene, while maintaining a moderate vector dose, new technologies for improved transgene presentation have been developed for adenoviral vaccine vectors.Areas covered: This review provides an overview of different genetic-fusion adjuvants that aim to improve antigen presentation in the context of adenoviral vector-based vaccines. The influence on both T cell and B cell responses are discussed, with a main focus on two technologies: MHC class II-associated invariant chain and virus-like-vaccines.Expert opinion: Different strategies have been tested to improve adenovirus-based vaccinations with varying degrees of success. The reviewed genetic adjuvants were designed to increase antigen processing and MHC presentation, or promote humoral immune responses with an improved conformational antigen display. While none of the introduced technologies is universally applicable, this review shall give an overview to identify potential improvements for future vaccination approaches.

Adenoviral vectored vaccines have shown considerable promise but could be improved by molecular adjuvants. Ligands in the TNF superfamily (TNFSF) are potential adjuvants for adenoviral vector (Ad5) vaccines based on their central role in adaptive immunity. Many TNFSF ligands require aggregation beyond the trimeric state (multi-trimerization) for optimal biological function. Here we describe Ad5 vaccines for HIV-1 Gag antigen (Ad5-Gag) adjuvanted with the TNFSF ligands 4-1BBL, BAFF, GITRL and CD27L constructed as soluble multi-trimeric proteins via fusion to Surfactant Protein D (SP-D) as a multimerization scaffold. Mice were vaccinated with Ad5-Gag combined with Ad5 expressing one of the SP-D-TNFSF constructs or single-chain IL-12p70 as adjuvant. To evaluate vaccine-induced protection, mice were challenged with vaccinia virus expressing Gag (vaccinia-Gag) which is known to target the female genital tract, a major route of sexually acquired HIV-1 infection. In this system, SP-D-4-1BBL or SP-D-BAFF led to significantly reduced vaccinia-Gag replication when compared to Ad5-Gag alone. In contrast, IL-12p70, SP-D-CD27L and SP-D-GITRL were not protective. Histological examination following vaccinia-Gag challenge showed a dramatic lymphocytic infiltration into the uterus and ovaries of SP-D-4-1BBL and SP-D-BAFF-treated animals. By day 5 post challenge, proinflammatory cytokines in the tissue were reduced, consistent with the enhanced control over viral replication. Splenocytes had no specific immune markers that correlated with protection induced by SP-D-4-1BBL and SP-D-BAFF versus other groups. IL-12p70, despite lack of anti-viral efficacy, increased the total numbers of splenic dextramer positive CD8+ T cells, effector memory T cells, and effector Gag-specific CD8+ T cells, suggesting that these markers are poor predictors of anti-viral immunity in this model. In conclusion, soluble multi-trimeric 4-1BBL and BAFF adjuvants led to strong protection from vaccinia-Gag challenge, but the protection was independent of standard immune markers. Soluble multi-trimeric SP-D-4-1BBL and SP-D-BAFF provide a novel technology to enhance adenoviral vector vaccines against HIV-1.

Background: The COVID-19 pandemic accelerated the development of diverse vaccine platforms, including mRNA, adenoviral vector, and protein subunit vaccines. Given the growing evidence that the gut microbiome modulates vaccine-induced immunity, this study compared the effects of a protein subunit vaccine (NVX-CoV2373), an mRNA vaccine (BNT162b2), and an adenoviral vector vaccine (ChAdOx1) on gut microbiome diversity following booster vaccination. Methods: We conducted a prospective cohort study involving 35 healthy adults who received an NVX-CoV2373 booster. Stool and blood samples were collected before vaccination and three weeks afterward. Gut microbiome profiles were analyzed using 16S rRNA gene sequencing, and the results were compared with our previous cohorts who received BNT162b2 or ChAdOx1 vaccines. Results: The NVX-CoV2373 booster was associated with a significant increase in the Shannon diversity index (p = 0.027), indicating enhanced alpha diversity. This finding contrasts with the decrease or absence of significant short-term change observed following repeated administrations of adenoviral vector and mRNA vaccines, respectively. Notably, NVX-CoV2373 vaccination was accompanied by an increased relative abundance of beneficial taxa such as Bacteroides fragilis and a decrease in Prevotella bivia. In comparison, repeated ChAdOx1 doses resulted in a sustained reduction in alpha diversity, whereas BNT162b2 showed a transient post-booster rise followed by a long-term decline in species richness. Conclusions: In the booster setting, the protein subunit vaccine NVX-CoV2373 exerted a distinct and favorable effect on gut microbiome diversity, increasing alpha diversity in contrast to the patterns observed with mRNA and adenoviral vector booster vaccines.

Objectives Many types of COVID19 vaccines are administered globally, yet there is not much evidence regarding their side effects among athletes. This study evaluated the selfreported postvaccination side effects of inactivated virus, adenoviral vector, and mRNA COVID19 vaccines among Algerian athletes. Methods A cross-sectional survey-based study was carried out in Algeria between March 01 and 4 April 2022. The study used a validated questionnaire with twenty-five multiple-choice items covering the participants’ anamnestic characteristics, post-vaccination side effects (their onset and duration), post-vaccination medical care, and risk factors. Results A total of 273 athletes completed the survey. Overall, (54.6%) of the athletes reported at least one local side effect, while (46.9%) reported at least one systemic side effect. These side effects were more prevalent among the adenoviral vector group compared to the inactivated virus and mRNA groups. The most common local side effect was injection site pain (29.9%), while Fever (30.8%) was the most prevalent systemic side effect. The age group of 31–40 years, allergy, previous infection with COVID-19, and the first dose of vaccines were associated with an increased risk of side effects for all groups of COVID-19 vaccines. Logistic regression analysis further revealed that compared to males, the incidence of reported side effects was significantly higher in females (odd ratio (OR) = 1.16; P = 0.015*) only for the adenoviral vector vaccine group. In addition, a significantly higher percentage of athletes group of high dynamic/moderate static or high dynamic /high static components suffered from post-vaccination side effects compared to the group of athletes with high dynamic/low static components (OR = 14.68 and 14.71; P < 0.001, respectively). Conclusions The adenoviral vector vaccines have the highest rate of side effects, followed by the inactivated virus and mRNA COVID-19 vaccines. COVID‑19 vaccines were well-tolerated among Algerian athletes and there were no reports of serious side effects. Nevertheless, further long-term follow-up study with a larger sample size of athletes (from different types and sports categories) is warranted to establish the long-term safety of the COVID-19 vaccine.

Increased Sensitivity of Radiated Murine Cervical Cancer Tumors to E7 Subunit Vaccine–driven CTL-mediated Killing Induces Synergistic Anti-tumor Activity

Comparison of vaccine-induced thrombotic events between ChAdOx1 nCoV-19 and Ad26.COV.2.S vaccines

As a member state of the European Union, where vaccines against COVID-19 are available and affordable, Bulgaria reports the lowest immunization coverage and the most pronounced vaccine distrust. The present study aimed to assess the self-reported adverse reactions following COVID-19 vaccination as a possible tool to increase the trust in vaccines. A cross-sectional survey-based study, covering 761 vaccinated respondents, was conducted in Plovdiv (469 with an mRNA vaccine and 292 with an adenoviral vector vaccine). Descriptive statistics parametric and non-parametric methods were applied. Statistical significance was set at p<0.05. The median age of the respondents was 42 years, females (72.5%). At least one adverse reaction was reported in 89.9% of those immunized with mRNA vaccine and 93.8% in the adenoviral vector vaccine group (p>0.05). They were mild to moderate and resolved within several days. The levels of local reactions were comparable: 91.7% in those who received mRNA and 89.7% in those who received an adenoviral vector vaccine (p = 0.366). The most common types of systemic reactions were fatigue, headache, and muscle pains. An association was found between the systemic reactions and the type of vaccine administered: 59.7% in mRNA recipients and 89.4% in adenoviral vector vaccinees (p<0.001). None of the registered systemic reactions required medical attention. There were 3 reports of generalized urticaria after an mRNA and 2 after an adenoviral vector vaccine. The reported reactions are relatively high but expected and no adverse events have been reported that are not listed in the official Summary of Product Characteristics.

Immunotherapy-induced CD8+ T Cells Instigate Immune Suppression in the Tumor

BackgroundSeveral cases of adverse reactions following vaccination for coronavirus disease 2019 (COVID-19) with adenoviral vector vaccines or mRNA-based vaccines have been reported to date. The underlying syndrome has been named “vaccine-induced immune thrombotic thrombocytopenia” (VITT) or “thrombosis with thrombocytopenia syndrome (TTS)” with different clinical manifestations.MethodsWe report the clinical course of five patients who had severe adverse reactions to COVID-19 vaccines, either with VITT/TTS, abdominal or pulmonary thrombosis after adenoviral vaccines, or Stevens' Johnson syndrome because of mRNA vaccination, all of whom required admission to the intensive care unit (ICU).ConclusionsAll patients with severe or life-threatening suspected reaction to different types of COVID-19 vaccination required ICU admission. A prompt evaluation of early symptoms and individualized clinical management is needed to improve outcomes.

IntroductionSolid-organ transplant (SOT) recipients have an excess mortality risk from severe acute respiratory syndrome coronavirus (SARS-CoV-2), while simultaneously initial reports have suggested blunted responses to messenger RNA (mRNA) vaccination. A...

Construction and Characterization of a Novel Recombinant Attenuated and Replication-Deficient Candidate Human Adenovirus Type 3 Vaccine: "Adenovirus Vaccine Within an Adenovirus Vector".

COVID-19 vaccination is a life-saving intervention. However, it does not come up without a risk of rare adverse events, which frequency varies between vaccines developed using different technological platforms. The increased risk of Guillain-Barré syndrome (GBS) has been reported for selected adenoviral vector vaccines but not for other vaccine types, including more widely used mRNA preparations. Therefore, it is unlikely that GBS results from the cross-reactivity of antibodies against the SARS-CoV-2 spike protein generated after the COVID-19 vaccination. This paper outlines two hypotheses according to which increased risk of GBS following adenoviral vaccination is due to (1) generation of anti-vector antibodies that may cross-react with proteins involved in biological processes related to myelin and axons, or (2) neuroinvasion of selected adenovirus vectors to the peripheral nervous system, infection of neurons and subsequent inflammation and neuropathies. The rationale behind these hypotheses is outlined, advocating further epidemiological and experimental research to verify them. This is particularly important given the ongoing interest in using adenoviruses in developing vaccines against various infectious diseases and cancer immunotherapeutics.