Analysis of virological response to therapy and resistance profile in treatment-experienced and naive HIV-1 infected Romanian patients receiving regimens containing darunavir boosted with ritonavir or cobicistat.

77% of Romanians infected with HIV receive antiretroviral therapy, with the challenge of maintaining long-term therapeutic success (the viral load becoming/remaining undetectable). The main purpose of this study was to provide comparative analysis of the long-term virological response to therapeutic regimens containing pharmacokinetically enhanced darunavir (DRV) with ritonavir (RTV) or cobicistat (COBI). The second aim was to evaluate the viral resistance profile to therapy, by number/type/frequency of viral mutations. This retrospective study was conducted on 462 patients infected with subtype F HIV-1, registered at the "Matei Bals" National Institute of Infectious Diseases, between 2018 and 2021: 384 patients received (among other ARV) DRV 600 mg, enhanced with RTV 100 mg (twice daily) and 78 patients received DRV 800 mg boosted with COBI 150 mg (once daily). The virological response was measured by determining the viral load (HIV-1 RNA copies/mL), while the incidence of viral resistance to therapy was assessed by genotyping tests. Comparing the patients with undetectable viremia, from the 1st visit to the 3rd one, the outcomes showed that at the last visit, 84.6% subjects in the DRV/c group achieved virological efficiency over those from DRV/r group (76.8%). The differences observed between this time points are statistically significant p < 0.05. DRV/c administered in combination with other ARV, in subtype F HIV-1 infected patients, proved to be more virologically effective, maintaining a favorable long-time result. When comparing the outcomes of the two groups, a statistically significant difference of p < 0.05 was obtained. 32 patients (27 from DRV/r group and 5 from DRV/c group) were evaluated with persistent HIV-1 ARN plasma load > 1000 copies/mL, during all 3 clinical visits. They formed a research sub-group evaluated in terms of resistance to therapy and were reported as virological failures. 28.12% of the sub-group with persistent HIV-1 RNA > 1000 copies/mL were from the DRV/r group and only 3.12% from the DRV/c group. Drug mutations (DRM) involved in antiretroviral resistance/sensitivity occurred both in the protease gene, and in the reverse transcriptase gene, with the involved ARV classes being protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors. 16 different types of mutations were evaluated in the PR gene and 20 mutations were evaluated in RT gene.

A heterologous prime-boost Ebola virus vaccine regimen induces durable neutralizing antibody response and prevents Ebola virus-like particle entry in mice.

Ebola virus (EBOV) is one of the most virulent pathogens known to humans. Neutralizing antibodies play a major role in the protection against EBOV infections. Thus, an EBOV vaccine capable of inducing a long-lasting neutralizing antibody response is highly desirable. We report here that a heterologous prime-boost vaccine regimen can elicit durable EBOV-neutralizing antibody response in mice. A chimpanzee serotype 7 adenovirus expressing EBOV GP (denoted AdC7-GP) was generated and used for priming. A truncated version of EBOV GP1 protein (denoted GP1t) was produced at high levels in Drosophila S2 cells and used for boosting. Mouse immunization studies showed that the AdC7-GP prime/GP1t boost vaccine regimen was more potent in eliciting neutralizing antibodies than either the AdC7-GP or GP1t alone. Neutralizing antibodies induced by the heterologous prime-boost regimen sustained at high titers for at least 18 weeks after immunization. Significantly, in vivo challenge studies revealed that the entry of reporter EBOV-like particles was efficiently blocked in mice receiving the heterologous prime-boost regimen even at 18 weeks after the final dose of immunization. These results suggest that this novel AdC7-GP prime/GP1t boost regimen represents an EBOV vaccine approach capable of establishing long-term protection, and therefore warrants further development.

An effective DNA priming-protein boosting approach for the cervical cancer vaccination.

Considerable advances have been made in developing human papillomaviruses (HPV) prophylactic vaccines based on L1 virus-like particles (VLPs). However, there are limitations in the availability of these vaccines in developing countries, where most cases of cervical cancer occur. In the current study, the prime-boost immunization strategies were studied using a DNA vaccine carrying HPV-16 L1 gene (pcDNA/L1) and insect cell baculovirus-derived HPV-16 L1 VLP. The humoral immunity was evaluated by measuring the specific IgG levels, and the T-cell immune response was assessed by measuring different cytokines such as IFN-γ, TNF-α and IL-10. Results showed that although immunization with pcDNA/L1 alone could induce strong cellular immune responses, higher immunogenicity especially antibody response was achieved in pcDNA/L1 priming-VLP boosting regimen. Therefore, we suggest that prime-boost regimen can be considered as an efficient prophylactic and therapeutic vaccine.