Virus World

Background: Unlike intramuscular vaccines, intranasal COVID-19 vaccines may generate mucosal immunity, which may be critical for to prevent infection and human-to-human transmission. We report interim immunogenicity and safety of an intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154, iNCOVACC®) in healthy adults compared with licensed intramuscular vaccine (Covaxin®).

Methods: In this open-label, multicentre, phase 3 clinical trial, healthy Indian adults were randomised to receive either two doses of BBV154 (n = 3,000) or Covaxin® (n = 160) 28 days apart. Primary immunogenicity outcome was geometric mean neutralisation antibody titres (PRNT50) against SARS-CoV-2 viruses; key secondary outcomes were safety and solicited adverse events, secretory-IgA and serum-IgA responses and cell-mediated immune responses.

Findings:We screened 3,209 volunteers between April 16 and June 4, 2022 and enrolled and randomised 3,160 to receive BBV154 (n = 2998) or Covaxin (n = 162). On Day 42, 14 days after the second dose, serum GMTs against ancestral (Wuhan) SARS-CoV-2 were 769 (95% CI: 665‒888) and 531 (426‒662) in BBV154 and Covaxin groups. The GMT ratio of 1·45 (95% CI: 1·11‒1·88) met the pre-defined superiority criterion for BBV154 over Covaxin. BBV154 also elicited a higher serum neutralising GMT [171 (137–213)] against Omicron BA.5 than Covaxin [82·4 (48·9–139)]. Similarly, at day 42 GMTs of secretory IgA were 12·3 (95% CI: 8·7 ‒17·4) and 6·6 (95% CI 4·6 ‒9·5) after BBV154 and Covaxin; BBV154 was superior to Covaxin with a GMT ratio of 1·9 (95% CI 1·1–3·0). BBV154 induced higher serum IgA titres and significantly higher levels of antibody-secreting plasmablasts on Day 42. Both vaccines induced equivalent T cell memory responses. Both vaccines were well tolerated, systemic adverse events were reported by 2·7% (82/2990) of BBV154 recipients and 6·2% (10/161) of Covaxin vaccinees. Nasal reactions were experienced by 4·9% (146/2990) of BBV154 participants, whereas 23·0% (37/161) of Covaxin® vaccinees experienced local injection site reactions.

Interpretation:Two intranasal doses of BBV154 were well tolerated with no safety concerns while eliciting superior humoral and mucosal immune responses compared with two intramuscular Covaxin injections. Further studies to assess the effect of BBV154 on infection and transmission are warranted.

Trial Registration: The trial was registered on the Indian Clinical Trials Registry India, CTRI/2022/02/40065, and ClinicalTrials.gov, NCT05522335.

Preprint at the Lancet available (Jan.31, 2023):

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4342771

NEW DELHI: The Drugs Controller General of India (DCGI) approved Bharat Biotech's Covid-19 recombinant nasal vaccine, health minister Mansukh Mandaviya tweeted on Tuesday. Notably, this will be India's first nasal vaccine for coronavirus. He took to Twitter, the health minister said, "Big Boost to India's Fight Against Covid-19! Bharat Biotech's ChAd36-SARS-CoV-S Covid-19 (Chimpanzee Adenovirus Vectored) recombinant nasal vaccine approved by @CDSCO_INDIA_INF for primary immunization against Covid-19 in 18+ age group for restricted use in emergency situation." "This step will further strengthen our collective fight against the pandemic. India has harnessed its science, R&D, and human resources in the fight against Covid-19 under PM @NarendraModi Ji's leadership," he added. He also said that we will defeat Covid-19 with a science-driven approach. "With the science-driven approach and Sabka Prayas, we will defeat Covid-19," he said. The regulator approved the vaccine for primary immunisation of those aged 18 years and above, for restricted use in emergency situations, Mandaviya added. The Hyderabad-based firm completed clinical trials of the nasal vaccine with about 4,000 volunteers and there is no side effect or adverse reaction reported so far, company sources had said.

Scientists hope the immunizations, delivered through the nose or mouth, will prevent even mild cases of illness.  Two needle-free COVID-19 vaccines that are delivered through the nose or mouth have been approved for use in China and India. China’s new vaccine, announced on Sunday, is inhaled through the nose and mouth as an aerosolized mist, and India’s, announced on Tuesday, is administered as drops in the nose. These mucosal vaccines target thin mucous membranes that line the nose, mouth and lungs. By prompting immune responses where SARS-CoV-2 first enters the body, mucosal vaccines could, in theory, prevent even mild cases of illness and block transmission to other people — something COVID-19 shots have been unable to do. Vaccines that produce sterilizing immunity would be game changing for the pandemic.  “These approvals validate the need for mucosal vaccines,” says Marty Moore, co-founder of Meissa Vaccines in Redwood City, California, which is developing a COVID-19 immunization that is delivered through the nose. “That’s the direction we need to go globally, and the United States needs to catch up.” The regulatory nods from China and India bring the number of approved COVID-19 mucosal vaccines in the world to four, including one already approved in Iran and another in Russia. More than 100 mucosal vaccines against the disease are in development globally, and about 20 have reached clinical trials in humans, according to Airfinity, a health-analytics company in London. Delivery methods include sprays, drops, aerosols and pills.

New arrivals

China’s inhaled vaccine, developed by CanSino Biologics in Tianjin, contains the same ingredients as the company’s COVID-19 shot that is already available in the country. A device called a nebulizer turns the liquid vaccine into an aerosol spray that is inhaled. China’s health department and National Medical Products Administration approved the vaccine to be used as a booster dose. India’s vaccine, developed by Bharat Biotech in Hyderabad, is approved as a two-dose primary inoculation, rather than a booster. Both companies have produced ‘viral vector’ vaccines that use a harmless adenovirus to deliver SARS-CoV-2 genetic material into host cells. Neither company has published phase III clinical-trial data, but both say they have completed those studies. Data from a phase II trial of CanSino’s inhaled vaccine found that, when given as a booster, the vaccine raised blood-serum antibody levels significantly more than did a boost from an injection. This suggests that the inhaled vaccine will offer protection that is as good as, or better than, that provided by the shot. Similarly, Bharat compared its intranasal vaccine to Covaxin, a COVID-19 jab available in India, by measuring antibody levels in the blood. The company did not release results of this study, but deemed the trial “successful”. Exactly how successful these vaccines will be is unclear. Expecting a vaccine to stop transmission of a virus or prevent even mild illness — achieving what is called sterilizing immunity — is a high bar. Bharat and CanSino won’t know whether their vaccines can achieve this until they have conducted further efficacy studies. Scant data are available on the efficacy of the two other mucosal COVID-19 vaccines. Iran approved a COVID-19 vaccine administered as a nasal spray and made by Razi Vaccine and Serum Research Institute in Karaj in October 2021. More than 5,000 doses have been delivered to the public. And Russia’s health ministry is reported to have approved an intranasal-spray version of Sputnik V, the country’s injected COVID-19 vaccine. Mucosal vaccines have been developed for other diseases, including polio, influenza and cholera. Most of these vaccines are taken orally, and one, against flu, is administered through the nose.