September 30, 2023

The coronavirus illness 2019 (COVID-19), which is brought on by an infection with the extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has already claimed greater than 6.8 million lives worldwide. Regardless of the fast improvement and widespread distribution of COVID-19 vaccines, the pandemic persists as a result of continuous emergence of latest SARS-CoV-2 variants.

Study: Immunogenicity and Tolerability of BBV154 (iNCOVACC®), an Intranasal SARS-CoV-2 Vaccine, Compared with Intramuscular Covaxin® in Healthy Adults: A Randomised, Open-Label, Phase 3 Clinical Trial. Image Credit: Dmitry Kovalchuk/Shutterstock
Research: Immunogenicity and Tolerability of BBV154 (iNCOVACC®), an Intranasal SARS-CoV-2 Vaccine, Compared with Intramuscular Covaxin® in Healthy Adults: A Randomised, Open-Label, Phase 3 Clinical Trial. Picture Credit score: Dmitry Kovalchuk/Shutterstock

A few of these variants, such because the Delta and Omicron variants of concern (VOCs), can evade the immune response induced by vaccination or pure an infection. Due to this fact, scientists want to enhance present vaccine formulations to supply higher safety towards SARS-CoV-2 an infection.


Most COVID-19 vaccines goal the spike protein of the ancestral SARS-CoV-2 pressure. As a result of presence of quite a few mutations on SARS-CoV-2 variant spike proteins, the efficacy of those vaccines has been considerably diminished.

SARS-CoV-2 should overcome each anatomical and immunological boundaries offered by the nasal mucosa to determine an infection. Mucosal immunity has an important position in blocking SARS-CoV-2 an infection to forestall its transmission; nonetheless, all at present obtainable COVID-19 intramuscular vaccines primarily elicit systemic immunity, with a restricted influence on mucosal immunity. 

An efficient intranasal vaccine may very well be extraordinarily useful in managing the COVID-19 pandemic by eliciting each mucosal protecting immunity on the web site of an infection and systemic immunity. Lately, Bharat Biotech Worldwide Restricted (BBIL) in India has developed BBV154. BBV154 is a chimpanzee adenoviral-vectored SARS-CoV-2 intranasal vaccine that encodes a prefusion-stabilized SARS-CoV-2 wild-type spike protein with two proline substitutions within the S2 subunit.

Preclinical animal research on mice, hamsters, rabbits, and rats have revealed that BBV154 induces robust mucosal and systemic humoral and cell-mediated immune responses.

In actual fact, a single intranasal dose of BBV154 elicited a superior immune response in extremely inclined K18-hACE2 99 transgenic mice as in comparison with the identical doses of COVID-19 intramuscular vaccines. Moreover, a single intranasal dose BBV154 in Syrian golden hamsters, K18-hACE2 transgenic mice, and rhesus macaques prevented the event of higher and decrease respiratory tract infections and irritation resulting from COVID-19.

Concerning the research

A current preprint research printed by The Lancet discusses the security profiles and immunogenicity of BBV154 in wholesome adults. These findings are primarily based on outcomes from a Part III, randomized, managed, open-label scientific trial that was carried out throughout hospitals in India.

The authors assessed the security, tolerability, and immunogenicity of BBV154 in wholesome adults, which included males and non-pregnant ladies, along with evaluating the efficacy of this vaccine with the licensed intramuscular vaccine, Covaxin.

All research members had been between 18 and 60 years of age on the time of recruitment. Not one of the research members beforehand obtained any COVID-19 vaccine or had a historical past of SARS-CoV-2 an infection.

Research findings

A complete of 3,209 members had been recruited between April 16, 2022, and June 4, 2022, 2,998 of whom had been randomized to obtain BBV154 and 162 to obtain Covaxin. 

Neutralization titers towards the ancestral SARS-CoV-2 pressure induced after two weeks of receiving the second dose of the intranasal BBV154 vaccine had been considerably increased as in comparison with these produced in Covaxin recipients beneath comparable situations.

Neutralization antibodies had been additionally detected three months after the primary dose of the BBV154 vaccine, thus confirming its sturdiness. The intranasal vaccine additionally elicited elevated cross-neutralization titers towards the Omicron variant BA.5 sub-lineage.

Sturdy mucosal antibodies within the type of secretory immunoglobulin A (sIgA) had been additionally detected in members who obtained the BBV154 vaccine on Day 42. The degrees of sIgA within the BBV154 group had been a lot increased as in comparison with the Covaxin group. This discovering was validated primarily based on the presence of statistically important IgA-secreting plasmablasts within the BBV154 group on Day 42 as in contrast with Day 0.

Each forms of COVID-19 vaccines had been nicely tolerated with low reactogenicity charges. Not one of the members reported any critical antagonistic results following vaccination.

For respiratory infections, mucosal immunization is related to a number of benefits as in comparison with standard intramuscular vaccination. For instance, mucosal IgA protects mucosal surfaces towards respiratory viruses by inhibiting their attachment to epithelial cells. Earlier research on influenza an infection have revealed that influenza-specific IgA is simpler in stopping an infection in people than influenza-specific IgG. 

SARS-CoV-2 initially infects the higher respiratory tract, which ends up in a rise in plasma IgA antibody ranges that bind to the virus and stop an infection. This highlights the essential position of IgA-mediated mucosal immunity towards COVID-19. 

IgA dimers discovered within the nasopharynx are considerably stronger than IgA monomers towards the identical goal. Due to this fact, secretory (dimeric) IgA may very well be simpler in defending towards SARS-CoV-2 an infection.


The BBV154 intranasal vaccine was discovered to be superior to the intramuscular Covaxin vaccine, as BBV154 induces increased ranges of IgG/IgA-secreting plasmablasts that correlate with elevated neutralization efficiency towards homologous and heterologous SARS-CoV-2 strains.

A number of the key benefits of BBV154 embody its non-invasiveness, ease of administration, improved affected person compliance, and health for mass vaccination. At present, additional scientific improvement of BBV154 is present process as part of a heterologous booster vaccination regime.

Journal reference:

  • Singh, C., Verma, S., Reddy, P., et al. (2023) Immunogenicity and Tolerability of BBV154 (iNCOVACC®), an Intranasal SARS-CoV-2 Vaccine, In contrast with Intramuscular Covaxin® in Wholesome Adults: A Randomised, Open-Label, Part 3 Medical Trial. Preprints with the Lancet. doi:10.2139/ssrn.4342771.