Introduction. Children are at a higher risk of influenza infection compared to the general population. The World Organization Health and recommendations of the Vaccine Advisory Committee of the Spanish Association of Pediatrics contemplate annual vaccination as the most effective way to prevent the disease. Therefore, the purpose of this review was to update information on efficacy and safety in the anti -shed vaccine in children and adolescents. Material and methods. A search in four electronic databases (Scopus, Cumulative Index to Nursing and Allied Health Literature, Medline / Pubmed, Google Scholar and Cochrane), as well as a manual search to identify original research published between 2012 and 2022. The guidelines of ANALYSIS (PRISMACR) as a preferred report element for systematic reviews. Results. Seven original research articles were included where two issues of antigripal vaccination were identified in healthy children/adolescents and with pathologies. The efficacy (between approximately 30% and 80%) varied depending on the vaccine used and circulating subtypes. Most adverse reactions were mild intensity, and the most common local adverse event was pain in the injection site. Conclusions. We positively highlight the safety of pediatric flu vaccination in analyzed studies, on the contrary, with respect to the efficacy of flu vaccination, we observe a wide variability of results. There is a clear need to continue conducting efficacy and safety studies in the child.

2022-10-01·Biotechnology and Bioengineering

Production of a high purity, C‐tagged hepatitis B surface antigen fusion protein VLP vaccine for malaria expressed in Pichia pastoris under cGMP conditions

Article

作者: Brod, Florian ; Jin, Jing ; Bolam, Emma J. ; Mukhopadhyay, Ekta ; Ashfield, Rebecca ; Berrie, Eleanor L. ; Angell‐Manning, Philip ; Tarrant, Richard D. ; Whale, Gary ; Green, Nicola ; Gilbert, Sarah C. ; Hobson, Mark ; Detmers, Frank J. ; Morris, Susan J. ; Hill, Adrian V. S. ; Draper, Simon J. ; Baleanu, Ioana N. ; Moyle, Sarah P.

AbstractVirus‐like particles (VLPs) induce strong humoral and cellular responses and have formed the basis of some currently licensed vaccines. Here, we present the method used for the production of R21, a VLP‐based anti‐sporozoite malaria vaccine, under current Clinical Good Manufacturing Practice regulations (cGMP). Previous preclinical studies in BALB/c mice showed that R21 produced almost complete protection against sporozoite challenge with transgenic Plasmodium berghei parasites. Here, we have modified the preclinical production process to enable the production of sufficient quantities of highly pure, clinical‐grade material for use in human clinical trials. The R21 construct was re‐engineered to include a C‐tag to allow affinity‐based separation from the major contaminant alcohol oxidase 1 (AOX 1, ~74 kDa). To our knowledge, this is the first use of C‐tag technology to purify a VLP vaccine candidate for use in human clinical trials. The R21 vaccine has shown high‐level efficacy in an African Phase IIb trial, and multiple clinical trials are underway to assess the safety and efficacy of the vaccine. Our findings support the future use of C‐tag platform technologies to enable cGMP‐compliant biomanufacturing of high purity yeast‐expressed VLP‐based vaccines for early phase clinical trials when clinical grade material is required in smaller quantities in a quick time frame.

2021-09-01·European Journal of Pharmacology3区 · 医学

Preclinical evidence of synergism between atovaquone and chemotherapy by AMPK-dependent mitochondrial dysfunction

3区 · 医学

Article

作者: Ma, Jingping ; Zhang, Han ; Tan, Hongxia ; Gong, Jianhua ; Xie, Fan

Chemoresistance has been associated with increased reliance on mitochondrial functions in many cancers, including lung cancer. Atovaquone is an anti-malaria drug and mitochondrial inhibitor. In this work, we attempted to explore whether atovaquone can be repurposed for lung cancer treatment to overcome chemoresistance. We showed that atovaquone inhibited proliferation, colony formation and survival in non-small cell lung cancer cell (NSCLC) cells. Of note, the effective dose of atovaquone was clinically achievable. Combination index value indicated that atovaquone and carboplatin were synergistic in inhibiting NSCLC. The potent efficacy of atovaquone and its synergism with chemotherapeutic drug were also demonstrated in NSCLC xenograft mice model. Mechanism studies showed that the synergism between atovaquone and carboplatin was due to atovaquone's ability in disrupting mitochondrial functions via specifically inhibiting complex III induced oxygen consumption. Subsequently, atovaquone activated AMP-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR) signaling. AMPK inhibition reversed the anti-NSCLC activity of atovaquone, suggesting that the action of atovaquone is also dependent on AMPK. Our work suggests that atovaquone is an attractive candidate for NSCLC treatment. Our findings emphasize that inhibition of mitochondrial function is a promising therapeutic strategy to enhance NSCLC chemosensitivity.

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