Baldwin, J. | Search bioRxiv

bioRxiv2021

Immunisation of ferrets and mice with recombinant SARS-CoV-2 spike protein formulated with Advax-SM adjuvant protects against COVID-19 infection

The development of a safe and effective vaccine is a key requirement to overcoming the COVID-19 pandemic. Recombinant proteins represent the most reliable and safe vaccine approach but generally require a suitable adjuvant for robust and durable immunity. We used the SARS-CoV-2 genomic sequence and in silico structural modelling to design a recombinant spike protein vaccine (Covax-19). A synthetic gene encoding the spike extracellular domain (ECD) was inserted into a baculovirus backbone to express the protein in insect cell cultures. The spike ECD was formulated with Advax-SM adjuvant and first tested for immunogenicity in C57BL/6 and BALB/c mice. The Advax-SM adjuvanted vaccine induced high titers of binding antibody against spike protein that were able to neutralise the original wildtype virus on which the vaccine was based as well as the variant B.1.1.7 lineage virus. The Covax-19 vaccine also induced potent spike-specific CD4+ and CD8+ memory T-cells with a dominant Th1 phenotype, and this was shown to be associated with cytotoxic T lymphocyte killing of spike labelled target cells in vivo. Ferrets immunised with Covax-19 vaccine intramuscularly twice 2 weeks apart made spike receptor binding domain (RBD) IgG and were protected against an intranasal challenge with SARS-CoV-2 virus 2 weeks after the second immunisation. Notably, ferrets that received two 25 or 50g doses of Covax-19 vaccine had no detectable virus in their lungs or in nasal washes at day 3 post-challenge, suggesting the possibility that Covax-19 vaccine may in addition to protection against lung infection also have the potential to block virus transmission. This data supports advancement of Covax-19 vaccine into human clinical trials.

immunology↗

bioRxiv2021

Accelerated vaccine induction of IgM neutralising antibody enables same day vaccine protection against a lethal influenza virus challenge

Novel influenza strains to which humans have no pre-existing immunity can trigger global pandemics without warning. Current pandemic vaccines typically require two doses and up to 6 weeks to induce protective immunity. In addition, to their role in increasing vaccine-induced immune response, adjuvants may also play a part in reducing the time between immunization and vaccine protection, although this role has seldom been previously explored in literature. This study assessed the speed of protection achievable with a standard inactivated influenza vaccine when formulated with or without a novel delta-inulin adjuvant (Advax). When formulated with Advax adjuvant mice were protected even when the vaccine was administered intramuscularly contemporaneously with a lethal intranasal virus challenge. The protection was found to be B-cell dependent and transfer of day 6 immune serum from mice immunised with Advax-adjuvanted influenza vaccine conferred protection to naive animals. This protection was shown to be mediated by vaccine induced IgM rather than IgG neutralising antibodies. The results show that influenza vaccine can be formulated to provide immediate protection following immunization with this novel concept warranting testing in human trials. IMPORTANCEIn the past 100 years there have been several major influenza pandemics that resulted in significant loss of life. The time taken for individuals to develop vaccine protection is an important factor in curbing the spread of infection and reducing pandemic mortality rates. Current influenza vaccines can take up to 5-6 weeks to generate full protection leaving front-line heath care workers and others, at risk for an extended period of time. Our novel accelerated vaccine protection approach provides effectively immediate vaccine protection against lethal virus challenge. This would assist front-line workers to continue to provide essential services and maintain critical infrastructure during pandemic. The study also highlights the often-overlooked role that antigen-specific IgM plays in virus protection and provides a novel adjuvanted strategy for enlisting IgM to provide accelerated vaccine protection.

microbiology↗