Design and computational evaluation of a novel multi-epitope hybrid vaccine against monkeypox virus: Potential targets and immunogenicity assessment for pandemic preparedness.

Monkeypox is a type of DNA-enveloped virus that belongs to the orthopoxvirus family, closely related to the smallpox virus. It can cause an infectious disease in humans known as monkeypox disease. Although there are multiple drugs and vaccines designed to combat orthopoxvirus infections, with a primary focus on smallpox, the recent spread of the monkeypox virus to over 50 countries have ignited a mounting global concern. This unchecked viral proliferation has raised apprehensions about the potential for a pandemic corresponding to the catastrophic impact of COVID-19. This investigation explored the structural proteins of monkeypox virus as potential candidates for designing a novel hybrid multi-epitope vaccine. The epitopes obtained from the selected proteins were screened to ensure their non-allergenicity, non-toxicity, and antigenicity to trigger T and B-cell responses. The interaction of the vaccine with toll-like receptor-3 (TLR-3) and major histocompatibility complexes (MHCs) was assessed using Cluspro 2.0. To establish the reliability of the docked complexes, a comprehensive evaluation was conducted using Immune and MD Simulations and Normal Mode Analysis. However, to validate the computational results of this study, additional in-vitro and in-vivo research is essential.

Development of conserved multi-epitopes based hybrid vaccine against SARS-CoV-2 variants: an immunoinformatic approach.

The world has faced unprecedented disruptions like global quarantine and the COVID-19 pandemic due to SARS-CoV-2. To combat these unsettling situations, several effective vaccines have been developed and are currently being used. However, the emergence of new variants due to the high mutation rate of SARS-CoV-2 challenges the efficacy of existing vaccines and has highlighted the need for novel vaccines that will be effective against various SARS-CoV-2 variants. In this study, we exploited the four structural proteins of SARS-CoV-2 to execute a potential multi-epitope vaccine against SARS-CoV-2 and its variants. The vaccine was designed by utilizing the antigenic, non-toxic, and non-allergenic B-cell and T-cell epitopes, which were selected from conserved regions of viral proteins. To build a vaccine construct, epitopes were connected through different linkers and an adjuvant was also attached at the start of the construct to enhance the immunogenicity and specificity of the epitopes. The vaccine construct was then screened through the aforementioned filters and it scored 0.6019 against the threshold of 0.4 on VexiJen 2.0 which validates its antigenicity. Toll-like receptors (i.e., TLR2, TLR3, TLR4, TLR5, and TLR8) and vaccine construct were docked by Cluspro 2.0, and TLR8 showed strong interaction with construct having a maximum negative binding energy of - 1577.1 kCal/mole. C-IMMSIM's immune simulations over three doses of the vaccine and iMODS' molecular dynamic simulations were executed to assess the reliability of the docked complexes. The stability of the vaccine construct was evaluated through the physicochemical analyses and the findings suggested that the manufactured vaccine is stable under a wide range of circumstances and can trigger immune responses against various SARS-CoV-2 variants (due to conserved epitopes). However, to strengthen the formulation of the vaccine and assess its safety and effectiveness, additional investigations and studies are required to support the computational data of this research at in-vitro and in-vivo levels. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00156-2.

Assessment of an Intra-Articular Drain in Arthroscopy-Assisted Anterior Cruciate Ligament Reconstruction.

Introduction The use of a drain after various types of arthroscopic surgeries has long been debated. Whether a drain offers an advantage in terms of pain, swelling, and functional outcome after arthroscopy-assisted reconstruction of the anterior cruciate ligament (ACL) needs to be investigated. This study was designed to assess the validity of the use of an intra-articular drain after routine arthroscopic ACL reconstruction and to assess the various complications associated with its use. Material and methods Forty-four patients (group I included patients for whom an intra-articular drain was used and group II included patients for whom an intra-articular drain was not used) diagnosed with ACL injury were included in the study. The patients in group I had a drain placed inside the joint, while those in group II had a drain placed outside the joint cavity but the drain placement was such that there remained no patient or observer bias. Results Outcome assessment was performed on days one, two, and three followed by weeks one, four, and eight, and six months after surgery by determining a visual analog pain (VAS) score. The assessment was also done for the range of motion (ROM) in terms of loss of flexion and extension with a hand-held goniometer, knee hemarthrosis, and thigh circumference. Although there was a difference in both the groups in terms of the above-mentioned parameters in the early post-operative period, the difference becomes insignificant at the final follow-up at six months. Conclusion From this study, we conclude that putting an intra-articular drain after ACL reconstruction offers no advantage in terms of functional outcome in the long term.