Publications by authors named "Rahul Chandrasekharan"
Article Synopsis
- During the development of recombinant vaccines, protein antigens can be destabilized by antimicrobial preservatives (APs), complicating understanding and analysis of their degradation.
- This study evaluates various analytical methods, specifically looking at HPV16 VLPs with different preservatives under accelerated conditions to assess structural integrity.
- The findings highlight that alternative approaches, like competitive ELISA and LC-MS peptide mapping, offer better insights into the molecular mechanisms of AP-induced destabilization compared to traditional methods.
This work describes Part 2 of multi-dose formulation development of a Human Papillomavirus (HPV) Virus-Like Particle (VLP) based vaccine (see Part 1 in companion paper). Storage stability studies with candidate multi-dose formulations containing individual or combinations of seven different antimicrobial preservatives (APs) were performed with quadrivalent HPV VLP (6, 11, 16, 18) antigens adsorbed to aluminum-salt adjuvant (Alhydrogel®). Real-time (up to two years, 2-8°C) and accelerated (months at 25 and 40°C) stability studies identified eight lead candidates as measured by antigen stability (competitive ELISA employing conformational serotype-specific mAbs), antimicrobial effectiveness (modified European Pharmacopeia assay), total protein content (SDS-PAGE), and AP concentration (RP-UHPLC).
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- Developing effective multi-dose subunit vaccines is tough due to the destabilizing effects of antimicrobial preservatives on protein antigens.
- This study focused on Human Papillomavirus (HPV) Virus-Like Particles (VLPs), testing various lower-concentration combinations of preservatives to balance antimicrobial action and antigen stability.
- Two screening methods, one-factor-at-a-time and statistical design-of-experiments, were employed, ultimately identifying 20 promising multi-dose vaccine formulations for further testing in long-term stability studies.
Introducing multi-dose formulations of Human Papillomavirus (HPV) vaccines will reduce costs and enable improved global vaccine coverage, especially in low- and middle-income countries. This work describes the development of key analytical methods later utilized for HPV vaccine multi-dose formulation development. First, down-selection of physicochemical methods suitable for multi-dose formulation development of four HPV (6, 11, 16, and 18) Virus-Like Particles (VLPs) adsorbed to an aluminum adjuvant (Alhydrogel®, AH) was performed.
View Article and Find Full Text PDFAuthorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain-hepatitis B surface antigen virus-like particle elicited protective immunity in cynomolgus macaques.
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