What is the mechanism of action of Covaxin (BBV152)?

Mechanism of Action of Covaxin (BBV152)

Covaxin (BBV152) is a whole-virion inactivated SARS-CoV-2 vaccine that works by presenting multiple viral antigens to the immune system, generating both humoral and cellular immune responses against various epitopes of the virus. 1, 2

Primary Components and Formulation

• Covaxin consists of inactivated (killed) SARS-CoV-2 viral particles combined with an adjuvant system 1
• The vaccine contains 6 μg of inactivated SARS-CoV-2 antigen adjuvanted with aluminum hydroxide gel (Algel) and/or Imidazoquinolin gallamide (IMDG), a TLR7/8 agonist 2
• Unlike vector-based or mRNA vaccines that focus primarily on the spike protein, Covaxin presents multiple viral antigens to the immune system, including both spike (S) and nucleocapsid (N) proteins 3

Immunological Response

Humoral Immunity

• Covaxin induces production of binding antibodies (IgG and IgA) against both spike and nucleocapsid antigens of SARS-CoV-2 3
• Neutralizing antibodies are generated that can recognize and bind to the virus, preventing its entry into host cells 3
• The antibody response has been shown to persist for at least 12 months post-vaccination against most SARS-CoV-2 variants 3

Cellular Immunity

• Covaxin generates spike-specific CD4+ and cytotoxic T-cell responses comparable to those induced by mRNA vaccines 4
• The T-cell response is predominantly Th1-biased, which is important for viral clearance 2

Advantages of Whole-Virion Approach

• By presenting multiple viral antigens rather than just the spike protein, Covaxin may potentially maintain efficacy against variants with significant mutations in the spike protein 1
• The inactivated virus platform has shown an excellent safety profile across different age groups, making it suitable for widespread use 5

Comparative Efficacy

• Phase III trials demonstrated approximately 80% efficacy for Covaxin compared to around 90% for adenovirus vector-based vaccines like Covishield 1
• When used as a booster, Covaxin generates lower anti-spike antibody titers compared to mRNA vaccines at day 28 (2004 IU/mL vs 26,669 IU/mL) and day 180 (4467 IU/mL vs 20,749 IU/mL) 4
• However, by day 360, anti-spike antibody titers and neutralizing antibody levels against Omicron subvariants become similar between Covaxin and mRNA vaccine recipients 4

Variant Coverage

• Covaxin induces neutralizing antibodies against multiple SARS-CoV-2 variants including ancestral (Wuhan), Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Delta Plus (B.1.617.2.1) 3
• However, neutralizing antibody levels against the Omicron variant have been consistently below detection limits except at 12 months post-vaccination 3

Clinical Implications

• The whole-virion approach of Covaxin may provide an advantage in maintaining efficacy against emerging variants with significant spike protein mutations 1
• The traditional inactivated vaccine platform makes Covaxin particularly suitable for use in low- and middle-income countries due to established manufacturing processes and storage requirements 3
• The vaccine has demonstrated good immunogenicity and safety profiles in both adults and children aged 2-18 years 5