Tuning the immune response: sulfated archaeal glycolipid archaeosomes as an effective vaccine adjuvant for induction of humoral and cell-mediated immunity towards the SARS-CoV-2 Omicron variant of concern

Abstract

Liposomes composed of sulfated lactosyl archaeol (SLA) have been shown to be a safe and effective vaccine adjuvant with a multitude of antigens in preclinical studies. In particular, SLA-adjuvanted SARS-CoV-2 subunit vaccines based on trimeric spike protein antigens were shown to be immunogenic and efficacious in mice and hamsters. With the continued emergence of SARS-CoV-2 variants, we sought to evaluate next-generation vaccine formulations with an updated antigenic identity. This was of particular interest for the widespread Omicron variant, given the abundance of mutations and structural changes observed within its spike protein compared to other variants. An updated version of our resistin-trimerized SmT1 corresponding to the B.1.1.529 variant was successfully generated in our Chinese Hamster Ovary (CHO) cell-based antigen production platform and characterized, revealing some differences in protein profile and ACE2 binding affinity as compared to reference strain-based SmT1. We next evaluated this Omicron-based spike antigen for its immunogenicity and ability to generate robust antigen-specific immune responses when paired with SLA liposomes or AddaS03 (a mimetic of the AS03 oil-in-water emulsion adjuvant system found in commercialized SARS-CoV-2 protein vaccines). Immunization of mice with vaccine formulations containing this updated antigen with either adjuvant stimulated neutralizing antibody responses favouring Omicron over the reference strain. Cell-mediated responses, which play an important role in the neutralization of intracellular infections, were induced to a much higher degree with the SLA adjuvant relative to the AddaS03-adjuvanted formulations. As such, updated vaccines that are better capable of targeting towards SARS-CoV-2 variants can be generated through an optimized combination of antigen and adjuvant components.

Preclinical evaluation of manufacturable SARS-CoV-2 spike virus-like particles produced in Chinese Hamster Ovary cells

“…The surrogate neutralization assay was performed as in ref. 24 and is described in the Supplementary Methods section .…”

Archaeal Lipid Vesicles as Immune Modulators, Adjuvants and Vaccine Carriers: A Review of the Past and Current Trends.

“…In more recent studies, researchers employed a semi-synthetic archaeal phospholipid (i.e., sulfated lactosyl archaeol) to encapsulate different antigens and to assess the potential of SLA glycolipid as an adjuvant system [75,76]. Their studies revealed that immunizing mice with variants of concern (VOC)-based vaccines, specifically Beta and Delta-based spike trimer antigens, resulted in improved neutralizing responses to spike proteins from the corresponding variant.…”

“…These researchers concluded that cell-mediated responses, which play important roles in the neutralization of intracellular infections, were stimulated to a significantly higher level with the SLA adjuvant when compared with the Adda S03-adjuvanted preparations. Consequently, further developed vaccines, which are better capable of targeting the SARS-CoV-2 variants, could be formulated via an optimized combination of adjuvant and antigen components [75,76].…”

A Broad-Spectrum Multi-Antigen mRNA/LNP-Based Pan-Coronavirus Vaccine Induced Potent Cross-Protective Immunity Against Infection and Disease Caused by Highly Pathogenic and Heavily Spike-Mutated SARS-CoV-2 Variants of Concern in the Syrian Hamster Model

“…This "copy-passed" vaccine strategy that "chased" the emerged VOC into a new batch of "improved" bivalent COVID-19 vaccines was often surpassed by fast-emerging and rapidly mutating Omicron lineages 13 . The sequences of Spike protein in the recently circulating EG.5, HV.1, and JN.1 Omicron subvariants have already undergone over 100 accumulated mutations, away from the recent XBB1.5-adapted bivalent vaccine 14,15,16 . The "improved" bivalent vaccine was only effective 4 to 29% against the Omicron subvariants, circulating in Winter 2022 14,15,16 , and its effectiveness decreased even further against the more recent divergent and highly transmissible EG.5, HV.1, and JN.1 Omicron subvariants, circulating in Winter pan-CoV vaccine strategy that incorporates highly conserved non-Spike antigens to induce broad, cross-protective immunity against past, present, and future VOCs 10,17,18 .…”