On average, there are 3–5 million severe cases of influenza virus infections globally each year. Seasonal influenza vaccines provide limited protection against divergent influenza strains. Therefore, the development of a universal influenza vaccine is a top priority for the NIH. Here, we report a comprehensive summary of all universal influenza vaccines that were tested in clinical trials during the 2010–2019 decade. Of the 1597 studies found, 69 eligible clinical trials, which investigated 27 vaccines, were included in this review. Information from each trial was compiled for vaccine target, vaccine platform, adjuvant inclusion, clinical trial phase, and results. As we look forward, there are currently three vaccines in phase III clinical trials which could provide significant improvement over seasonal influenza vaccines. This systematic review of universal influenza vaccine clinical trials during the 2010–2019 decade provides an update on the progress towards an improved influenza vaccine.

Unlike many other viruses, HIV-1 is highly variable. The structure of the viral envelope changes as the infection progresses and is one of the biggest obstacles in developing an HIV-1 vaccine. HIV-1 infection can cause the production of various natural autoantibodies, including catalytic antibodies hydrolyzing DNA, myelin basic protein, histones, HIV-integrase, HIV-reverse transcriptase, β-casein, serum albumin, and some other natural substrates. Currently, there are various directions for the development of HIV-1 vaccines: stimulation of the immune response on the mucous membranes; induction of cytotoxic T cells, which lyse infected cells and hold back HIV-infection; immunization with recombinant Env proteins or vectors encoding Env; mRNA-based vaccines and some others. However, despite many attempts to develop an HIV-1 vaccine, none have been successful. Here we review the entire spectrum of antibodies found in HIV-infected patients, including neutralizing antibodies specific to various viral epitopes, as well as antibodies formed against various autoantigens, catalytic antibodies against autoantigens, and some viral proteins. We consider various promising targets for developing a vaccine that will not produce unwanted antibodies in vaccinated patients. In addition, we review common problems in the development of a vaccine against HIV-1.

The influenza virus continually evolves because of the high mutation rate, resulting in dramatic changes in its pathogenicity and other biological properties. This study aimed to evaluate the evolution of certain essential properties, understand the connections between them, and find the molecular basis for the manifestation of these properties. To that end, 21 A(H1N1)pdm09 influenza viruses were tested for their pathogenicity and toxicity in a mouse model with a ts/non-ts phenotype manifestation and HA thermal stability. The results demonstrated that, for a strain to have high pathogenicity, it must express a toxic effect, have a non-ts phenotype, and have a thermally stable HA. The ancestor A/California/07/2009 (H1N1)pdm influenza virus expressed the non-ts phenotype, after which the cycling trend of the ts/non-ts phenotype was observed in new strains of A(H1N1)pdm09 influenza viruses, indicating that the ratio of the ts phenotype will increase in the coming years. Of the 21 tested viruses, A/South Africa/3626/2013 had the high pathogenicity in the mouse model. Sequence alignment analysis showed that this virus has three unique mutations in the polymerase complex, two of which are in the PB2 gene and one that is in the PB1 gene. Further study of these mutations might explain the distinguishing pathogenicity.

The Epstein–Barr virus (EBV) is the first human herpesvirus identified as an oncogenic agent, with approximately 95% of adults worldwide being latently infected. EBV infection is associated with multiple diseases, including nasopharyngeal carcinoma, Hodgkin’s lymphoma, infectious mononucleosis, and multiple sclerosis. Given significant EBV-associated disease burden, developing effective vaccines against EBV remains a priority. In this review, we first presented the current understanding of EBV biology and pathogenesis, focusing on its biological structure and immune evasion mechanisms, and discussed key viral antigens—including gp350, gp42, gH/gL, and latency proteins—as potential targets for EBV vaccine development. We also summarized recent advances in various EBV vaccine platforms, including subunit, viral vector-based, nanoparticle-based, and mRNA vaccines, and discussed the related preclinical and clinical evidence, although no effective EBV vaccine has been approved for clinical use yet. In summary, this review provides an overview of the current landscape in EBV vaccine research, and sheds new light on developing new therapeutic approaches against EBV-associated diseases.

Understanding the mechanisms of virus-host interactions is crucial for advancing our knowledge of viral pathogenesis and developing effective antiviral strategies. As novel, highly virulent pathogens continue to emerge, overcoming the challenges in virus-host biology and infection control is more important than ever. The CRISPR-Cas system has revolutionized genetic engineering, offering a precise and efficient application in synthetic biology. It is also invaluable in virology research, diagnostics, and antiviral therapeutics. In this review, we explore the latest advances in CRISPR-Cas-based approaches to elucidate virus-host interactions, focusing on the identification of key receptors and host factors essential for virus infection. Furthermore, we discuss the potential of the CRISPR-Cas system as an antiviral strategy for tackling newly emerging and re-emerging viruses. Finally, we discuss the potential of CRISPR-Cas-based gene editing for the development of innovative viral vaccines.

The generation of pandemic influenza A viruses of the previous century as well as that of the current influenza A/H1N1/2009 pandemic appear to be governed and preceded by reassortment events in other mammalian species. So far, it could not be shown that transmission of avian influenza viruses to humans will directly cause a pandemic. Zoonotic transmissions of avian and also of porcine influenza viruses of diverse subtypes have been repeatedly described. However, these events did not lead to further spread and establishment of these viruses. This is in contrast to the current A/H1N1/2009 viruses which already have started to outcompete seasonal human influenza viruses. The actual molecular key factors required for a successful exchange of genome segments between different influenza virus strains and which factors foster the consecutive spread of certain reassortant viruses in the human population remain to be pinpointed. It has been elucidated so far that newly introduced genome segments need to be compatible with both the remaining original segments and the human hosts.

Highly pathogenic avian influenza viruses (HPAIV) originate from avirulent precursors but differ from all other influenza viruses by the presence of a polybasic cleavage site in their hemagglutinins (HA) of subtype H5 or H7. In this study, we investigated the ability of a low-pathogenic avian H5N1 strain to transform into an HPAIV. Using reverse genetics, we replaced the monobasic HA cleavage site of the low-pathogenic strain A/Teal/Germany/Wv632/2005 (H5N1) (TG05) by a polybasic motif from an HPAIV (TG05poly). To elucidate the virulence potential of all viral genes of HPAIV, we generated two