Attacking global pandemics, cancer, and rare diseases with lipid-based adjuvant systems

Posted on April 01, 2022


Adjuvant Product Spotlight April 2022

Vaccine research has been rapidly increasing since the early 1990s. Between 1993 and 1997, less than 20,000 papers and patents were published related to vaccines. Fast forward twenty years, between 2013 and 2017, nearly 90,000 papers and patents were published related to vaccines (Global Science and Technology Trends Report, CAS, n.d.). And with the recent COVID-19 pandemic and subsequent race to find a vaccine, these numbers are sure to soar even higher between 2018 and 2022. The COVID-19 pandemic solidified Avanti’s claim as a leader in lipid-based drug delivery solutions. But lipid nanoparticles aren’t the only important lipid-based tool of ours that vaccines commonly employ. So, let’s dive into some recent research showing the wide application range of our liposomal adjuvant systems, particularly our synthetic monophosphoryl lipid A (MPLA), PHAD®.

MPLA-Adjuvanted Liposomes as a Potent Subunit Vaccine Against SARS-CoV-2 and Its Variants

As SARS-CoV-2 continues to mutate and more variants are formed, the need for a vaccine to effectively treat them remains necessary. Ideal targets have been identified for a subunit vaccine to combat SARS-CoV-2 and its variants such as S1, S2, S-trimer, S-ECD, and RBD domains of the SARS-Cov-2 virus. Protein-based vaccines targeting these domains are different from the nucleic-acid-based vaccines currently being used to combat the pandemic. Nucleic-acid-based vaccines have been highly effective and in the early days of the pandemic, had a speed advantage. Protein-based vaccines could offer potential advantages like being more costly to manufacture, easier to store, and the ability to be used in a wider population for a better safety profile.

One disadvantage of protein-based vaccines is their relatively weak immunogenicity. The solution to the weak immunogenicity is an immunostimulant – in this case, lipid-based adjuvants! MPLA was investigated as a Toll-like receptor (TLR) agonist adjuvant additive and compared to another TLR agonist, Pam3CSK4. This study proved that MPLA-adjuvanted vaccines elicited a stronger humoral and cellular immune response than Pam3CSK4 and even traditional Alum. They also showed that the choice of antigen combined with liposomal MPLA made a major difference in vaccine efficacy. S-trimer/MPLA and RBD/MPLA vaccines were able to effectively neutralize SARS-Cov-2, whereas S1/MPLA and S-ECD/MPLA were only moderately able to neutralize the virus. Together, this information presents a promising method for further development of subunit vaccines capable of neutralizing SARS-CoV-2 and its variants.

References:

Wang, J. et. al. MPLA-Adjuvanted Liposomes Encapsulating STrimer or RBD or S1, but Not S‑ECD, Elicit Robust Neutralization Against SARS-CoV‑2 and Variants of Concern. (2021). https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.1c02025

MPLA-Enveloped Gold Nanocages for Immunogenic Phototherapy of Aggressive Melanoma

Avanti’s liposomal adjuvant systems are also being investigated as a treatment for melanoma. Melanoma is a dangerous form of skin cancer, and an effective treatment needs to not only remove the primary tumor, but also inhibit metastasis and recurrence of the cancer. Photodynamic therapies (PDTs) have emerged as a non-invasive form of treatment for superficial tumors. One difference between melanoma and other tumors is the high level of melanin production. Melanin absorbs visible light and can inhibit deep penetration of therapeutic light. New photosensitizers are characterized by their near-infrared absorption feature, making the new generation of photosensitizers viable as PDT for melanoma.

Research conducted at the Huazhong University of Science and Technology recently proved MPLA bilayer-enveloped and photosensitizer-loaded gold nanocages (MLI-AuNCs) to be a viable and promising form of treatment for melanoma. The thermosensitive lipid bilayer led to strong biocompatibility and bioavailability with high tumor accumulation. Using near-infrared radiation on the MLI-AuNCs in melanoma tumors resulted in complete removal of the primary tumor combined with a robust antitumor immune response with the help of MPLA released in situ. The MLI-AuNC PDT therapy proved to promote the infiltration of T-lymphocytes for long lasting antitumor immunity.

References:

\Xie, J. et. al. Photosensitizer-loaded gold nanocages for immunogenic phototherapy of aggressive melanoma. (2022). https://www.sciencedirect.com/science/article/abs/pii/S1742706122000629?via%3Dihub

MPLA-Adjuvanted Nano-Multilamellar Vesicles as an Anti-Chikungunya Virus Vaccine

The Chikungunya virus (CHIKV) is transmitted to humans through the bite of a mosquito. Symptoms of CHIKV are most commonly fever and joint pain which typically subside within a week. In some cases, joint pain can be severe and even disabling and persist for months. Currently, there are no preventative vaccines or treatment medications available for CHIKV. Although rare, outbreaks of CHIKV do occur, most commonly in Africa, Asia, South America, and the Indian subcontinent. In 2017, Pakistan had an outbreak and reported over 8000 cases. Outbreaks were more severe in India (62,000) and South America/Caribbean (185,000). There have also been lesser outbreaks reported in Sudan (2018), Yemen (2019), and Cambodia and Chad (2020). Brazil has had a particularly hard time with CHIKV accounting for over 90% of the cases reported from South America/Caribbean in 2017 (WHO, 2020).

Researchers at the University of Sao Paulo, Brazil set out to find a treatment for CHIKV. CHIKV is a virus with a single stranded RNA genome that is translated into four non-structural and five structural proteins. Of particular interest is the structural protein Glycoprotein E2 due to its involvement in binding to host cell receptors. As previously discussed, protein-based subunit vaccines tend to elicit a weaker immune response than nucleic-acid-based vaccines and must be enhanced with adjuvants and efficient delivery systems. In this case, nano-multilamellar vesicles loaded with the lipid adjuvant MPLA was capable of inducing immunogenicity of the target antigen which led to the induction of virus-neutralizing antibodies. These promising results set the stage for future work towards a CHIKV vaccine, and further studies investigating nano-multilamellar vesicles as antigen delivery systems.

References:

Venceslau-Carvalho, A. et. al. Nano-multilamellar lipid vesicles loaded with a recombinant form of the chikungunya virus E2 protein improve the induction of virus-neutralizing antibodies. (2021). Nanomedicine: Nanotechnology, Biology, and Medicine. https://linkinghub.elsevier.co...

WHO website link

Trust Avanti with Your Lipid-Based Adjuvant Needs

If you’re conducting vaccine research, you can’t leave anything to chance. When you choose Avanti, you are choosing the highest quality lipid-based adjuvants on the market. With unparalleled purity and customer service, you can rest easy knowing your research project is being fueled with nothing less than the best. To learn more about Avanti’s lipid-based adjuvants, click HERE! If you would like to discuss your vaccine project with our Formulations experts, click HERE! And if you’ve read this far, you know that people do amazing things with our lipids. What will you do?