Introduction: The incidence of human papillomavirus 16 (HPV16)-associated head and neck squamous-cell carcinoma (HNC) is steadily rising. Intranasal neoadjuvant vaccines against HNC are a novel and potentially highly effective approach in cancer immunotherapy to directly induce broad humoral and cellular mucosal immunity.

Method: We utilized our previously reported Qβ-HPVag consisting of virus-like particles loaded with CPG and chemically coupled to four elongated HPV16-derived E6/E7 MHCI peptides for intranasal administration in an orthotopic murine model. Our study encompasses a range of in vivo and in vitro experiments, as well as tissue imaging mass cytometry (ongoing), to evaluate the immune cell populations within the tumor microenvironment.

Results: Our preliminary results indicated that intranasal administration of Qβ-HPVag impeded orthotopic tumor growth and enhanced the infiltration of tumor-infiltrating lymphocytes in the tumor. Assessment of vaccinated mouse lungs showed an increased CD8 T cell population, suggesting a protective potential of the intranasal vaccine. Moreover, our findings demonstrated improved tumor-free survival in the treated group after primary tumor dissection, indicating the efficacy of the neoadjuvant approach.

Conclusion: Our preliminary findings demonstrate the effectiveness of intranasal vaccination using Qβ-HPVag in an orthotopic murine model of aggressive head and neck cancer. These promising outcomes pave the way for novel clinical development strategies in HNC immunotherapy, suggesting a potential transformative impact on treatment paradigms.

Introduction: Recent research demonstrates that specific variants of gamma delta (γδ) T cells possess innate properties, previously deemed only adaptative. Our understanding of the innate-like behavior of γδ T cells upon encountering virus-like nanoparticles (VLPs) remains limited. Exploring the interaction between γδ T cells and VLPs presents an intriguing avenue for research, offering insights into how VLPs can serve as an effective platform to enhance their expansion and activation. Methods: We created novel plant-derived VLPs, engineered to incorporate TLR ligands to effectively stimulate the innate immune system. This study encompasses in vivo and in vitro assays, FC analysis and RNA sequencing. Results: Our findings demonstrate the robust uptake of our novel VLPs by γδ T cells, leading to significant expansion in draining lymph nodes upon subcutaneous injection. Interestingly, in mice lacking TLR7 or C3, γδ T cell expansion was reduced, suggesting their involvement in the immune response triggered by our VLPs. Subsequent analysis of γδ T cell Vγ1 and Vγ4 subtypes post-VLP administration revealed substantial expansion and distinct activation profiles. Ongoing RNA sequencing will unveil activation pathways, shedding light on the molecular mechanisms underlying their response to our innovative VLPs. Conclusion: Our novel data reveal the innate-like response of γδ T cells to our VLPs, loaded with different innate stimuli. This highlights the rapid and crucial role of γδ T cells in early immune responses, offering insights for potential immunotherapeutic strategies against cancer.

Ruminants, both domestic and wild, are the primary sources of Q fever, a zoonosis that causes reproductive abnormalities in animals and acute (self-limiting flu-like syndromes) and chronic (pneumonia, hepatitis, and endocarditis) conditions in people. The disease affects people and domestic ruminants globally, with vaccination being the primary method of control and management. Coxevac is the only approved vaccine for preventing Q fever in ruminants. This phase I vaccination greatly decreases the risk of miscarriage and shedding. Vaccination against Q fever has not been shown to be effective in buffalo, despite their extensive farming in several countries. This study used phase-specific ELISAs to assess the humoral response and its impact on abortion rates in buffalo. A total of 35 water buffalo were inoculated with two doses of a commercial vaccine and screened for phase I and II antibodies. Seroreactivity increased significantly between t0 and t1, and decreased somewhat between t1 and t2. Seroconversion did not differ substantially by age or natural infection status. At t1 and t2, naturally pre-infected animals showed somewhat greater reactivity than negative animals, but no significant differences were found. Animals over 20 months demonstrated higher seroreactivity at t1 compared to younger animals, but the difference was not statistically significant. Herd research found that immunization lowered miscarriage and placenta retention rates. The impact of immunization on miscarriage rates was reported regularly. In June, herd research showed 19 placenta retentions and 3 miscarriages due to Coxiella burnetii, which was detected using specialized real-time PCR. After five months after immunization, only five placenta retentions and one miscarriage occurred.
Preliminary evidence suggests that vaccination can be effective in buffalo, even in seropositive animals. However, further research is needed to fully understand the dynamics of seroconversion in this species.

In many countries, a booster dose against COVID-19 is recommended to reduce the risk of complications and death. A prospective epidemiological study of patients with COVID-19 who were previously vaccinated against the disease was conducted to compare those with a booster dose and those without. We analyzed 390 patients with COVID-19, hospitalized in various structures of the University Hospital "St. George”, in the city of Plovdiv, between October 2021 and April 2022, previously vaccinated against SARS-CoV-2. Only 12.1% (n=390) of all patients with COVID-19 (n=2835) were vaccinated. Onset of illness and hospitalization were, on average, 5.6 months after a full vaccination course. The average age of hospitalized vaccinated patients was 64.8 years (+-standard deviation 16.2) with a median of 69 years and a range of 15-95 years. The number of those with booster doses was 61 (15.6%). The data on fatal cases showed that 91.4% were unvaccinated and 8.6% were fully vaccinated. The average age of deceased vaccinated patients was 74 years, and they had 2.21 accompanying diseases. The booster dose reduces the risk of death by 2.5 times compared to the full vaccination course. The present epidemiological study confirms the importance of vaccination and revaccination against SARS-CoV-2. The ratio between vaccinated and unvaccinated hospitalized patients shows that the available vaccines against the disease in Bulgaria protect against severe complications and death.