Covid-19 and Influenza Oral Vaccine Study

A Binded, Randomised, Controlled Cross-over Trial to Assess the Safety and Efficacy of Mucosal Covid-19 and Influenza Vaccines

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.

Study Overview

• Status: Recruiting
• Conditions: Influenza, Human; covid19 Infection
• Intervention / Treatment: Biological: Covid-19 vaccine; Biological: Influenza vaccine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sharen Pringle, GradCert; Phone Number: 0437033400; Email: office@arasmi.org

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5042
      • Recruiting
      • ARASMI
      • Contact: Sharen Pringle, GradCert; Phone Number: 0437033400; Email: office@arasmi.org
      • Principal Investigator: Dimitar Sajkov, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Able to provide written informed consent
• Males or females 18 years of age or older
• Understand and are likely to comply with planned study procedures and be available for all study visits.
• Do not plan to have a non-study COVID-19 or influenza vaccine within the next 6 months.

Exclusion Criteria:

• Allergy to COVID-19 or seasonal influenza vaccine or one of its components e.g. polysorbate 80.
• Have received a COVID-19 or influenza vaccine or an experimental agent within 30 days prior to the study vaccination or expect to receive another experimental agent or a COVID-19 or influenza vaccine during the trial reporting period.
• Any serious medical, social or mental condition which, in the opinion of the investigator, would be detrimental to the subjects or the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Covid-19 vaccine group; Subjects in this group will receive two sublingual doses of COVID-19 vaccine two weeks apart. Three months after the second dose they will receive two sublingual doses of influenza vaccine two weeks apart.	Biological: Covid-19 vaccine; Recombinant SARS-CoV-2 spike protein with Advax-CpG55.2 adjuvant; Other Names: SARS-CoV-2 vaccine; Biological: Influenza vaccine; Inactivated seasonal influenza vaccine with Advax-CpG55.2 adjuvant
Experimental: Influenza vaccine group; Subjects in this group will receive two sublingual doses of influenza vaccine two weeks apart. Three months after the second dose they will receive two sublingual doses of COVID-19 vaccine two weeks apart.	Biological: Covid-19 vaccine; Recombinant SARS-CoV-2 spike protein with Advax-CpG55.2 adjuvant; Other Names: SARS-CoV-2 vaccine; Biological: Influenza vaccine; Inactivated seasonal influenza vaccine with Advax-CpG55.2 adjuvant
Experimental: Combined vaccine group; Subjects in this group will receive two sublingual doses of combined COVID-19 and influenza vaccine two weeks apart. Three months after the second dose they will receive two sublingual doses of placebo vaccine two weeks apart.	Biological: Covid-19 vaccine; Recombinant SARS-CoV-2 spike protein with Advax-CpG55.2 adjuvant; Other Names: SARS-CoV-2 vaccine; Biological: Influenza vaccine; Inactivated seasonal influenza vaccine with Advax-CpG55.2 adjuvant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SARS-CoV-2 Seroconversion	Proportion of study participants who seroconvert (4-fold or greater rise in serum spike antibody) by primary vaccine group	Between baseline and 2 weeks post the second dose
Influenza Seroconversion	Proportion of study participants who seroconvert (4-fold or greater rise in hemagglutinin antibody) by primary vaccine group	Between baseline and 2 weeks post the second dose
SARS-CoV-2 Seroprotection	Proportion of study participants who achieve a spike protein neutralisation titer of 32 or greater by primary vaccine group	Between baseline and 2 weeks post the second dose
Influenza Seroprotection	Proportion of study participants who achieve a hemagglutinin neutralisation titer of 40 or greater by primary vaccine group	Between baseline and 2 weeks post the second dose
SARS-CoV-2 Geometric mean titer fold change	Increase in Geometric mean titer of spike neutralisation antibodies by primary vaccine group	Between baseline and 2 weeks post the second dose
Influenza geometric mean titer fold change	Increase in Geometric mean titer of spike neutralisation antibodies by primary vaccine group	Between baseline and 2 weeks post the second dose
Safety assessment 1	Frequency of Adverse events by primary vaccine group	Between time of administration of first dose and through study completion, an average of 10 months
Safety assessment 2	Frequency of Serious Adverse events by primary vaccine group	Between time of administration of first dose and through study completion, an average of 10 months
SARS-CoV-2 infection	Frequency of SARS-CoV-2 infections in study participants by primary vaccine group, age, gender, co-morbidities, and past infection	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Influenza infection	Frequency ofinfluenza infections in study participants by primary vaccine group, age, gender, co-morbidities, and past infection	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody durability	The proportion of subjects who remain seroprotected throughout the duration of the study including broken down by primary vaccine group.	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Seroconversion in participants with and without evidence of past infection	Antibody seroconversion in participants by primary vaccine group	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Antibody GMT in participants with and without evidence of past infection	Antibody GMT in baseline seropositive versus negative participants by primary vaccine group.	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months
Antibody correlates of protection	antibody levels in subjects with or without breakthrough infection	From 2 weeks post the administration of the second dose and through study completion, an average of 10 months

Collaborators and Investigators

• Sponsor: Vaxine Pty Ltd
• Collaborators: Australian Respiratory and Sleep Medicine Institute Ltd
• Investigators: Principal Investigator: Dimitar Sajkov, MBBS/PhD, ARASMI

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 7, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: vaccine; influenza; adjuvant; covid-19; pandemic; mucosal; spikogen; advax
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Influenza, Human; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Influenza Vaccines; COVID-19 Vaccines
• Other Study ID Numbers: Vaxine-2301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD with external researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No