The SARS-CoV-2 outbreak has caused millions of deaths globally. It has a particularly
high mortality rate in elderly people and those with chronic disease. SARS-COV-2 vaccines
remain a key priority to help fight the current pandemic as they help reduce symptomatic
infection and disease severity. However, vaccine immunity starts to wane as early as 3
months following the most recent immunisation. This rapidly waning vaccine immunity is a
particular problem for the newer Omicron variants. Spikogen® vaccine is an Advax-CpG55.2
adjuvanted recombinant protein vaccine that was shown to significantly reduce infection
and serious disease in a pivotal Phase 3 trial in 16,876 participants who received two
intramuscular doses 3 weeks apart. SpikoGen® vaccine was licensed for use in the Middle
East as a primary vaccine course in adults in October 2021. Eight million doses of
SpikoGen® vaccine have subsequently been supplied to date. A booster study confirmed the
safety and immunogenicity of SpikoGen® vaccine when given as a third dose intramuscular
booster to adult participants who previously received two doses of either inactivated
viral vaccine, adenoviral vector vaccine, mRNA or recombinant protein vaccine. While
COVID-19 vaccines such as SpikoGen® vaccine have been shown to reduce the incidence of
severe SARS-CoV-2 infection disease, they have less effect on SARS-CoV-2 infection or
transmission. This is because intramuscular vaccines largely work by increasing antibody
and T cell levels within the body, whereas what is needed to prevent infection and
transmission is mucosal immunity, which means increasing immunity at the body surfaces
where the virus initially gets access to the body, namely the mucosal surfaces of the
nose and upper respiratory tract. To induce mucosal immunity normally requires immune
cells at these respiratory tract surfaces to be exposed to the relevant viral antigen,
which requires the vaccine to be applied to these surfaces in such a way as to trigger an
appropriate immune response.The current study is based on the finding that an adjuvanted
protein-based COVID-19 vaccine (SpikoGen®) when given as 2 sublingual doses 2 weeks apart
in monkeys that had previously received a primary course of 2 intramuscular doses of the
same vaccine, was safe and well tolerated and induced robust protection against challenge
with the heterologous Omicron BA.5 virus. The monkeys that received the sublingual boost
also showed reduced nasal virus shedding (additional details in the Investigator
Brochure). This suggests an oral/ sublingual COVID-19 vaccine may also help block virus
transmission. Similarly, mice that received sublingual inactivated influenza vaccine with
Advax-CpG adjuvant have demonstrated robust protection against an otherwise lethal
influenza infection. The purpose of the current study is to assess the effectiveness of
protein-based COVID-19 or influenza vaccines when given individually or together via
oral/ sublingual mucosal route instead of intramuscular delivery. The comparator will be
a seasonal influenza vaccine which will also be administered with Advax-CpG adjuvant via
the oral route. This study will use a cross-over design and everyone in the study will
over a space of about 4 months receive both the COVID-19 and influenza vaccines.