Human Tick-Borne Diseases and Advances in Anti-Tick Vaccine Approaches: A Comprehensive Review.

This comprehensive review explores the field of anti-tick vaccines, addressing their significance in combating tick-borne diseases of public health concern. The main objectives are to provide a brief epidemiology of diseases affecting humans and a thorough understanding of tick biology, traditional tick control methods, the development and mechanisms of anti-tick vaccines, their efficacy in field applications, associated challenges, and future prospects. Tick-borne diseases (TBDs) pose a significant and escalating threat to global health and the livestock industries due to the widespread distribution of ticks and the multitude of pathogens they transmit. Traditional tick control methods, such as acaricides and repellents, have limitations, including environmental concerns and the emergence of tick resistance. Anti-tick vaccines offer a promising alternative by targeting specific tick proteins crucial for feeding and pathogen transmission. Developing vaccines with antigens based on these essential proteins is likely to disrupt these processes. Indeed, anti-tick vaccines have shown efficacy in laboratory and field trials successfully implemented in livestock, reducing the prevalence of TBDs. However, some challenges still remain, including vaccine efficacy on different hosts, polymorphisms in ticks of the same species, and the economic considerations of adopting large-scale vaccine strategies. Emerging technologies and approaches hold promise for improving anti-tick vaccine development and expanding their impact on public health and agriculture.

BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine.

Recent publications have explored intranasal (i.n.) adenovirus-based (Ad) vaccines as an effective strategy for SARS-CoV-2 in pre-clinical models. However, the effects of prior immunizations and infections have yet to be considered. Here, we investigate the immunomodulatory effects of Mycobacterium bovis BCG pre-immunization followed by vaccination with an S-protein-expressing i.n. Ad, termed Ad(Spike). While i.n. Ad(Spike) retains some protective effect after 6 months, a single administration of BCG-Danish prior to Ad(Spike) potentiates its ability to control viral replication of the B.1.351 SARS-CoV-2 variant within the respiratory tract. Though BCG-Danish did not affect Ad(Spike)-generated humoral immunity, it promoted the generation of cytotoxic/Th1 responses over suppressive FoxP3+ TREG cells in the lungs of infected mice. Thus, this vaccination strategy may prove useful in limiting future pandemics by potentiating the long-term efficacy of mucosal vaccines within the context of the widely distributed BCG vaccine.

A novel intradermal tattoo-based injection device enhances the immunogenicity of plasmid DNA vaccines.

In recent years, tattooing technology has shown promising results toward evaluating vaccines in both animal models and humans. However, this technology has some limitations due to variability of experimental evaluations or operator procedures. The current study evaluated a device (intradermal oscillating needle array injection device: IONAID) capable of microinjecting a controlled dose of any aqueous vaccine into the intradermal space. IONAID-mediated administration of a DNA-based vaccine encoding the glycoprotein (GP) from the Ebola virus resulted in superior T- and B-cell responses with IONAID when compared to single intramuscular (IM) or intradermal (ID) injection in mice. Moreover, humoral immune responses, induced after IONAID vaccination, were significantly higher to those obtained with traditional passive DNA tattooing in guinea pigs and rabbits. This device was well tolerated and safe during HIV vaccine delivery in non-human primates (NHPs), while inducing robust immune responses. In summary, this study shows that the IONAID device improves vaccine performance, which could be beneficial to the animal and human health, and importantly, provide a dose-sparing approach (e.g., monkeypox vaccine).

Two DNA vaccines protect against severe disease and pathology due to SARS-CoV-2 in Syrian hamsters.

The SARS-CoV-2 pandemic is an ongoing threat to global health, and wide-scale vaccination is an efficient method to reduce morbidity and mortality. We designed and evaluated two DNA plasmid vaccines, based on the pIDV-II system, expressing the SARS-CoV-2 spike gene, with or without an immunogenic peptide, in mice, and in a Syrian hamster model of infection. Both vaccines demonstrated robust immunogenicity in BALB/c and C57BL/6 mice. Additionally, the shedding of infectious virus and the viral burden in the lungs was reduced in immunized hamsters. Moreover, high-titers of neutralizing antibodies with activity against multiple SARS-CoV-2 variants were generated in immunized animals. Vaccination also protected animals from weight loss during infection. Additionally, both vaccines were effective at reducing both pulmonary and extrapulmonary pathology in vaccinated animals. These data show the potential of a DNA vaccine for SARS-CoV-2 and suggest further investigation in large animal and human studies could be pursued.

Transient Liver Damage and Hemolysis Are Associated With an Inhibition of Ebola Virus Glycoprotein-Specific Antibody Response and Lymphopenia.

Numerous studies have demonstrated the importance of the adaptive immunity for survival following Ebola virus (EBOV) infection. To evaluate the contribution of tissue damage to EBOV-induced immune suppression, acute liver damage or hemolysis, 2 symptoms associated with lethal EBOV infection, were chemically induced in vaccinated mice. Results show that either liver damage or hemolysis was sufficient to inhibit the host humoral response against EBOV glycoprotein and to drastically reduce the level of circulating T cells. This study thus provides a possible mechanism for the limited specific antibody production and lymphopenia in individuals with lethal hemorrhagic fever infections.

A novel DNA platform designed for vaccine use with high transgene expression and immunogenicity.

The development of new, low-cost vaccines and effective gene therapies requires accurate delivery and high-level expression of candidate genes. We developed a plasmid vector, pIDV-II, that allows for both easy manipulation and high expression of exogenous genes in mammalian cells. This plasmid is based upon the pVax1 plasmid and shares a common structure with typical mammalian transcription units. It is composed of a chicken ß-actin promoter (CAG), followed by an intron and flanked by two restriction sites, and also includes a post-transcriptional regulatory element, followed by a transcriptional termination signal. While the modification of pVax1 elements either decreased eGFP expression levels or had no effect at all, replacement of the promoter, the poly-A signal, deletion of the T7 and AmpR promoters, and inversion of the ORI-Neo/Kan cassette, significantly increased in vitro eGFP expression with the modified plasmid called pIDV-II. To further evaluate our vector, expression levels of three viral antigens were compared in cell lines transfected either with pVax1 or pCAGGS backbones as controls. Higher transgene expression was consistently observed with pIDV-II. The humoral and cellular responses generated in mice immunized with pIDV-II vs pVax1 expressing each viral antigen individually were superior by 2-fold or more as measured by ELISA and ELISPOT assays. Overall these results indicate that pIDV-II induces robust transgene expression, with concomitant improved cellular and humoral immune responses against the transgene of interest over pVax1. The new vector, pIDV-II, offers an additional alternative for DNA based vaccination and gene therapy for animal and human use.

Mutation Signatures and In Silico Docking of Novel SARS-CoV-2 Variants of Concern.

One year since the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China, several variants of concern (VOC) have appeared around the world, with some variants seeming to pose a greater thread to public health due to enhanced transmissibility or infectivity. This study provides a framework for molecular characterization of novel VOC and investigates the effect of mutations on the binding affinity of the receptor-binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2) using in silico approach. Notable nonsynonymous mutations in RBD of VOC include the E484K and K417N/T that can be seen in South African and Brazilian variants, and N501Y and D614G that can be seen in all VOC. Phylogenetic analyses demonstrated that although the UK-VOC and the BR-VOC fell in the clade GR, they have different mutation signatures, implying an independent evolutionary pathway. The same is true about SA-VOC and COH-VOC felling in clade GH, but different mutation signatures. Combining molecular interaction modeling and the free energy of binding (FEB) calculations for VOC, it can be assumed that the mutation N501Y has the highest binding affinity in RBD for all VOC, followed by E484K (only for BR-VOC), which favors the formation of a stable complex. However, mutations at the residue K417N/T are shown to reduce the binding affinity. Once vaccination has started, there will be selective pressure that would be in favor of the emergence of novel variants capable of escaping the immune system. Therefore, genomic surveillance should be enhanced to find and monitor new emerging SARS-CoV-2 variants before they become a public health concern.