scholarly journals Novel Concepts for HIV Vaccine Vector Design

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Quazim A. Alayo ◽  
Nicholas M. Provine ◽  
Pablo Penaloza-MacMaster

ABSTRACT The unprecedented challenges of developing effective vaccines against intracellular pathogens such as HIV, malaria, and tuberculosis have resulted in more rational approaches to vaccine development. Apart from the recent advances in the design and selection of improved epitopes and adjuvants, there are also ongoing efforts to optimize delivery platforms. The unprecedented challenges of developing effective vaccines against intracellular pathogens such as HIV, malaria, and tuberculosis have resulted in more rational approaches to vaccine development. Apart from the recent advances in the design and selection of improved epitopes and adjuvants, there are also ongoing efforts to optimize delivery platforms. Viral vectors are the best-characterized delivery tools because of their intrinsic adjuvant capability, unique cellular tropism, and ability to trigger robust adaptive immune responses. However, a known limitation of viral vectors is preexisting immunity, and ongoing efforts are aimed at developing novel vector platforms with lower seroprevalence. It is also becoming increasingly clear that different vectors, even those derived from phylogenetically similar viruses, can elicit substantially distinct immune responses, in terms of quantity, quality, and location, which can ultimately affect immune protection. This review provides a summary of the status of viral vector development for HIV vaccines, with a particular focus on novel viral vectors and the types of adaptive immune responses that they induce.

Author(s):  
Zuzana Strizova ◽  
Jitka Smetanova ◽  
Jirina Bartunkova ◽  
Tomas Milota

The number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients keeps rising in most of the European countries despite the pandemic precaution measures. The current antiviral and anti-inflammatory therapeutic approaches are only supportive, have limited efficacy, and the prevention in reducing the transmission of SARS-CoV-2 virus is the best hope for public health. It is presumed that an effective vaccination against SARS-CoV-2 infection could mobilize the innate and adaptive immune responses and provide a protection against severe forms of coronavirus disease 2019 (COVID-19) disease. As the race for the effective and safe vaccine has begun, different strategies were introduced. To date, viral vector-based vaccines, genetic vaccines, attenuated vaccines, and protein-based vaccines are the major vaccine types tested in the clinical trials. Over 80 clinical trials have been initiated; however, only 18 vaccines have reached the clinical phase II/III or III, and 4 vaccine candidates are under consideration or have been approved for the use so far. In addition, the protective effect of the off-target vaccines, such as <i>Bacillus</i> Calmette-Guérin and measles vaccine, is being explored in randomized prospective clinical trials with SARS-CoV-2-infected patients. In this review, we discuss the most promising anti-COVID-19 vaccine clinical trials and different vaccination strategies in order to provide more clarity into the ongoing clinical trials.


EBioMedicine ◽  
2021 ◽  
Vol 68 ◽  
pp. 103410
Author(s):  
Stine SF Nielsen ◽  
Line K Vibholm ◽  
Ida Monrad ◽  
Rikke Olesen ◽  
Giacomo S Frattari ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2109
Author(s):  
Samuel T. Pasco ◽  
Juan Anguita

Vaccine design traditionally focuses on inducing adaptive immune responses against a sole target pathogen. Considering that many microbes evade innate immune mechanisms to initiate infection, and in light of the discovery of epigenetically mediated innate immune training, the paradigm of vaccine design has the potential to change. The Bacillus Calmette-Guérin (BCG) vaccine induces some level of protection against Mycobacterium tuberculosis (Mtb) while stimulating trained immunity that correlates with lower mortality and increased protection against unrelated pathogens. This review will explore BCG-induced trained immunity, including the required pathways to establish this phenotype. Additionally, potential methods to improve or expand BCG trained immunity effects through alternative vaccine delivery and formulation methods will be discussed. Finally, advances in new anti-Mtb vaccines, other antimicrobial uses for BCG, and “innate memory-based vaccines” will be examined.


2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Byeonghwi Lim ◽  
Sangwook Kim ◽  
Kyu-Sang Lim ◽  
Chang-Gi Jeong ◽  
Seung-Chai Kim ◽  
...  

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) infection is the most important viral disease causing severe economic losses in the swine industry. However, mechanisms underlying gene expression control in immunity-responsible tissues at different time points during PRRSV infection are poorly understood. We constructed an integrated gene co-expression network and identified tissue- and time-dependent biological mechanisms of PRRSV infection through bioinformatics analysis using three tissues (lungs, bronchial lymph nodes [BLNs], and tonsils) via RNA-Seq. Three groups with specific expression patterns (i.e., the 3-dpi, lung, and BLN groups) were discovered. The 3 dpi-specific group showed antiviral and innate-immune signalling similar to the case for influenza A infection. Moreover, we observed adaptive immune responses in the lung-specific group based on various cytokines, while the BLN-specific group showed down-regulated AMPK signalling related to viral replication. Our study may provide comprehensive insights into PRRSV infection, as well as useful information for vaccine development.


2019 ◽  
Vol 7 (10) ◽  
pp. 402
Author(s):  
Titus Abiola Olukitibi ◽  
Zhujun Ao ◽  
Mona Mahmoudi ◽  
Gary A. Kobinger ◽  
Xiaojian Yao

In the prevention of epidemic and pandemic viral infection, the use of the antiviral vaccine has been the most successful biotechnological and biomedical approach. In recent times, vaccine development studies have focused on recruiting and targeting immunogens to dendritic cells (DCs) and macrophages to induce innate and adaptive immune responses. Interestingly, Ebola virus (EBOV) glycoprotein (GP) has a strong binding affinity with DCs and macrophages. Shreds of evidence have also shown that the interaction between EBOV GP with DCs and macrophages leads to massive recruitment of DCs and macrophages capable of regulating innate and adaptive immune responses. Therefore, studies for the development of vaccine can utilize the affinity between EBOV GP and DCs/macrophages as a novel immunological approach to induce both innate and acquired immune responses. In this review, we will discuss the unique features of EBOV GP to target the DC, and its potential to elicit strong immune responses while targeting DCs/macrophages. This review hopes to suggest and stimulate thoughts of developing a stronger and effective DC-targeting vaccine for diverse virus infection using EBOV GP.


Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6459-6468 ◽  
Author(s):  
Ashley T. Martino ◽  
Masataka Suzuki ◽  
David M. Markusic ◽  
Irene Zolotukhin ◽  
Renee C. Ryals ◽  
...  

AbstractAlthough adeno-associated viral (AAV) vectors have been successfully used in hepatic gene transfer for treatment of hemophilia and other diseases in animals, adaptive immune responses blocked long-term transgene expression in patients on administration of single-stranded AAV serotype-2 vector. More efficient vectors have been developed using alternate capsids and self-complimentary (sc) genomes. This study investigated their effects on the innate immune profile on hepatic gene transfer to mice. A mild and transient up-regulation of myeloid differentiation primary response gene (88), TLR9, TNF-α, monocyte chemotactic protein-1, IFN-γ inducible protein-10, and IFN-α/β expression in the liver was found after single-stranded AAV vector administration, regardless of the capsid sequence. In contrast, scAAV vectors induced higher increases of these transcripts, upregulated additional proinflammatory genes, and increased circulating IL-6. Neutrophil, macrophage, and natural killer cell liver infiltrates were substantially higher on injection of scAAV. Some but not all of these responses were Kupffer cell dependent. Independent of the capsid or expression cassette, scAAV vectors induced dose-dependent innate responses by signaling through TLR9. Increased innate responses to scAAV correlated with stronger adaptive immune responses against capsid (but not against the transgene product). However, these could be blunted by transient inhibition of TLR9.


2021 ◽  
Vol 12 ◽  
Author(s):  
Indumathi Manoharan ◽  
Puttur D. Prasad ◽  
Muthusamy Thangaraju ◽  
Santhakumar Manicassamy

For decades, lactate has been considered an innocuous bystander metabolite of cellular metabolism. However, emerging studies show that lactate acts as a complex immunomodulatory molecule that controls innate and adaptive immune cells’ effector functions. Thus, recent advances point to lactate as an essential and novel signaling molecule that shapes innate and adaptive immune responses in the intestine and systemic sites. Here, we review these recent advances in the context of the pleiotropic effects of lactate in regulating diverse functions of immune cells in the tissue microenvironment and under pathological conditions.


Vaccine ◽  
2016 ◽  
Vol 34 (19) ◽  
pp. 2188-2196 ◽  
Author(s):  
Kate H. Gartlan ◽  
George Krashias ◽  
Frank Wegmann ◽  
William R. Hillson ◽  
Erin M. Scherer ◽  
...  

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