Combined Hormonal Contraception and the Adenoviral Vector Covid-19 Vaccines

There are at least 4 different types of covid-19 vaccines that are available worldwide. The most widely used ones are the mRNA genetic vaccine and the viral vector vaccine. In the midst of the COVID-19 pandemic and after the administration of millions of those vaccines globally over few months, several national health authorities across Europe decided to pause the administration of the chimpanzee adenovirus-vectored vaccine1 (ChAdOx1nCoV-19, AZD1222; Oxford/AstraZeneca) after sporadic reports of severe cases of thrombocytopenia, bleeding, or thrombosis in those who received this vaccine. This complication has been identified as Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) that affects mostly woman under the age of 55 years at a rate of 1:100,000 vaccine doses. Combined hormonal contraceptives (CHC) are known to carry the risk of thrombosis in certain high-risk population. Accordingly, women taking those contraceptives raised their concern of getting such vaccine. This review will attempt to explain the different mechanisms of thrombosis which abolish any link between the VITT complication and the use of CHC. Reassuring statements from authoritative agencies are also included.

Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties

Adenovirus vector-based genetic vaccines have emerged as a powerful strategy against the SARS-CoV-2 health crisis. This success is not unexpected because adenoviruses combine many desirable features of a genetic vaccine. They are highly immunogenic and have a low and well characterized pathogenic profile paired with technological approachability. Ongoing efforts to improve adenovirus-vaccine vectors include the use of rare serotypes and non-human adenoviruses. In this review, we focus on the viral capsid and how the choice of genotypes influences the uptake and subsequent subcellular sorting. We describe how understanding capsid properties, such as stability during the entry process, can change the fate of the entering particles and how this translates into differences in immunity outcomes. We discuss in detail how mutating the membrane lytic capsid protein VI affects species C viruses’ post-entry sorting and briefly discuss if such approaches could have a wider implication in vaccine and/or vector development.

The Safe Baculovirus-Based PrM/E DNA Vaccine Protected Fetuses Against Zika Virus in A129 Mice

The Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family of enveloped RNA viruses. The correlation between viral infection and fetal microcephaly was revealed in 2015, yet we still lack a vaccine against ZIKV. Here, we present a genetic vaccine that delivers the premembrane (prM) and envelope (E) genes of ZIKV using a recombinant baculovirus vector that expresses a human endogenous retrovirus (HERV) envelope on its surface to enhance gene delivery. We observed that baculoviruses with HERV envelopes (AcHERV) exhibited specifically higher gene transfer efficiency in human cells compared to the wild-type baculovirus vector. Using the AcHERV baculovirus vector, we constructed a recombinant baculovirus vaccine encoding ZIKV prM/E genes (AcHERV-ZIKV), which are major targets of neutralizing antibodies. Mice immunized twice with AcHERV-ZIKV exhibited high levels of IgG, neutralizing antibodies, and IFN-γ. In challenge tests in IFN knock-out mice (A129), AcHERV-ZIKV showed complete protection in both challenge and pregnancy tests. These results suggest that AcHERV-ZIKV could be a potential vaccine candidate for human application.

Capsid and Genome Modification Strategies to Reduce the Immunogenicity of Adenoviral Vectors

Adenovirus-based gene transfer vectors are the most frequently used vector type in gene therapy clinical trials to date, and they play an important role as genetic vaccine candidates during the ongoing SARS-CoV-2 pandemic. Immediately upon delivery, adenovirus-based vectors exhibit multiple complex vector-host interactions and induce innate and adaptive immune responses. This can severely limit their safety and efficacy, particularly after delivery through the blood stream. In this review article we summarize two strategies to modulate Ad vector-induced immune responses: extensive genomic and chemical capsid modifications. Both strategies have shown beneficial effects in a number of preclinical studies while potential synergistic effects warrant further investigations.

Skin immunization for effective treatment of multifocal melanoma refractory to PD1 blockade and Braf inhibitors

BackgroundDespite the remarkable benefits associated with the interventional treatment of melanomas (and other solid cancers) with immune checkpoint and Braf inhibitors (Brafi), most patients ultimately progress on therapy. The presence of multifocal/disseminated disease in patients increases their mortality risk. Hence, the development of novel strategies to effectively treat patients with melanomas that are resistant to anti-PD1 mAb (αPD1) and/or Brafi, particularly those with multifocal/disseminated disease remains a major unmet clinical need.MethodsMice developing induced/spontaneous BrafV600E/Pten−/− melanomas were treated by cutaneous immunization with a DNA vaccine encoding the melanoma-associated antigen TRP2, with Brafi or αPD1 alone, or with a combination of these treatments. Tumor progression, tumor-infiltration by CD4+ and CD8+ T cells, and the development of TRP2-specific CD8+ T cells were then monitored over time.ResultsVaccination led to durable antitumor immunity against PD1/Brafi-resistant melanomas in both single lesion and multifocal disease models, and it sensitized PD1-resistant melanomas to salvage therapy with αPD1. The therapeutic efficacy of the vaccine was associated with host skin-resident cells, the induction of a systemic, broadly reactive IFNγ+CD8+ T cell repertoire, increased frequencies of CD8+ TIL and reduced levels of PD1hi/intCD8+ T cells. Extended survival was associated with improved TIL functionality, exemplified by the presence of enhanced levels of IFNγ+CD8+ TIL and IL2+CD4+ TIL.ConclusionsThese data support the use of a novel genetic vaccine for the effective treatment of localized or multifocal melanoma refractory to conventional αPD1-based and/or Brafi-based (immune)therapy.

DNA Vaccination Target on Amyloid Oligomer also Reduce tau Pathology and Improve Synaptic Function in Aged 3xTg-AD Mice

Background: Active immunotherapy has been widely used as a potential therapeutic method for both treatment and prevention of Alzheimer’s disease (AD). Amyloid deposition and tau hyperphosphorylation are main pathological hallmarks of AD. Reduction in both is required to regulate synaptic proteins neurotransmission which can finally protect cognitive function. Growing evidence suggests that the most toxic β-Amyloid peptide (Aβ) oligomers can be detected from the very beginning of AD development, so it is wise for us to develop effective therapy method focus on Aβ oligomers rather than monomers. Methods: The 3×Tg-AD mice were randomly divided into two groups immunized with p(Aβ3–10)10-MT and PBS respectively. The PBS group was used for positive group while C57/B6 mice was used for negative group. ELISA was used to detect the antibody titers and Morris Water Maze was to analysis the cognitive function. The Aβ ,Tau hyperphosphorylation, Neuron and synaptic protein were detected through immunohistochemistry and western blot. Results: Mice immunized with p(Aβ3–10)10-MT can not only reduce the levels of Aβ oligomers and plaque deposits but also protect neuron as well as synaptic function, finally prevent the decline spatial memory in transgenic mice. Conclusions: Our novel DNA genetic vaccine is highly safe and effective, thus providing strong evidence for the treatment and prevention of early AD.

Nanotherapeutic systems for delivering cancer vaccines: recent advances

With an increase in the global burden of cancer-related deaths, the quest for developing new therapeutic solutions has taken momentum. In this regard, the idea of using cancer vaccines came to existence approximately 30 years ago, where gene therapy interventions have shown significant improvement in the therapeutic outcomes against several types of cancers. Cancer vaccines usually encounter a number of challenges with limited targeting ability to the tumors. Nanocarriers have been studied as a technological innovation for tumor targeting of gene therapeutics. This article provides a critical insight into the recent progress made in nanotherapeutic strategies for genetic vaccine delivery for treatment against various types of cancers. Moreover, the article intends to provide a summary of the research work being done on this topic.