Recently, the Lancet magazine preprint platform SSRN published the world's first inhaled COVID-19 vaccine heterologous enhancement data online.
In the study, Zhu Fengcai's team from the Jiangsu Provincial Center for Disease Control and Prevention used a random, non-blind, parallel-controlled clinical study of the inhaled adenovirus vector COVID-19 vaccine Kwesa (hereinafter referred to as "Kwesa inhaled") developed by CanSino Biologics Co., Ltd. (hereinafter referred to as "CanSino Biologics", 688185.SH, 06185.HK) in adults aged 18 years and older who have completed 2 doses of inactivated vaccine basal immunity, with the aim of evaluating the safety and immunogenicity enhanced by 1 dose of Kwesa xogenous enhancement.
The above-mentioned study found that in adults aged 18 years and older who have completed 2 doses of inactivated COVID-19 vaccination, 1 dose of inhaled adenovirus vector COVID-19 vaccine Kwesa is used as heterologous enhancement, which is safe and highly immunogenic, and can induce higher levels of neutralizing antibodies than homologous enhancement with inactivated vaccines.
It is worth noting that in November 2021, the world's first inhaled COVID-19 vaccine was unveiled at the "2021 Fifth Hainan International Health Industry Expo", and the audience can experience the use of inhaled COVID-19 vaccines on the spot. It is understood that the inhaled NEW CROWN vaccine uses the same vaccine as intramuscular injection, and its formulation has not changed, only using different modes of administration. Nebulized inhalation immunity uses nebulizers to atomize vaccines into tiny particles that enter the respiratory tract and lungs through oral inhalation, thereby stimulating mucosal immunity, which cannot be brought about by intramuscular injection.
The study enrolled a total of 420 participants in Jiangsu who had completed the 2-dose inactivated vaccination procedure, randomly assigned to three groups of 140 people in each group, who were boosted by low-dose inhalation of Kwesa (0.1 ml), high-dose inhalation of Kwesa (0.2 ml) and intramuscular inactivated vaccine.
The safety data disclosed in the study showed that the incidence of adverse reactions after xogenous enhancement with inhaled Kwesa was lower than that of homologous enhancement with inactivated vaccines. 28 days after the intensive vaccination, no serious adverse reactions occurred in the inhalation group, and no clinically significant lung function abnormalities occurred in the inhalation group at different doses, which fully verified the safety of the inhalation dosage form.
The immunogenicity results disclosed in the study showed that after inhalation enhancement, the neutralizing antibody level was significantly higher than the inactivated vaccine homologous enhancement. There was no significant difference in the immune response in the high- and low-dose inhalation groups, and during the 14 days and 28 days after strengthening, they were 6.7-10.7 times higher than those in the inactivated homologous enhancement group, respectively. After inhalation boosting, neutralizing antibody levels peaked on day 28, with low doses of 60541 (95% CI 4584.1, 7995.0) and high doses of 4221.3 (2976.9, 5985.3) IU/ml, which stimulated neutralizing antibody levels significantly higher than other heterologous booster immune programs. In addition, inhaled Kwesa also has a high level of cross-protection against Delta mutant strains, neutralizing antibody levels higher than inactivated vaccines.
Strengthens pre- and post-immune neutralizing antibody levels
Studies have shown that the RBD-specific ELISA antibody level induced by inhalation heterologous enhancement is significantly higher than that of inactivated vaccine homologous enhancement, and 28 days after strengthening, the RBD antibody level in the low-dose inhalation group is about 13 times that of inactivated vaccine homologous enhancement.
Significantly increased ENZYME-linked immune spot reactions of IFN-γ and IL-2 specific for THEX spike proteins can be detected 7 days after inactivation enhancement with inhalation form enhancement. The infγ and IL-2 expression levels of the inhalation form booster group were 6-10 times and 4-5 times higher than those in the inactivated vaccine booster group, respectively. The data showed that compared with the homologous enhancement of inactivated vaccines, heterologous enhancement with inhalation dosage forms could significantly induce the cellular immune response of Th1 type, while factors such as sex and age had no effect on the cellular immune response.
Strengthens the level of T cell immune response before and after immunity
The available data show that inhalation with Kwesa trains the body's immune memory function by mimicking the natural infection of the virus, which can not only stimulate humoral and cellular immunity, but also efficiently induce mucosal immunity to achieve triple comprehensive protection. The above studies have shown that inactivated vaccines with inhaled Kwesa can stimulate a strong mucosal immune response. 14 days after vaccination, laboratory testing of RBD-specific IgA-binding antibody levels in the serum of subjects showed that inhalation dosage form xogenous enhancement IgA levels were about 6-9 times that of inactivated vaccine homologous enhancement.
The above results confirm that the inhalation of Kwesa with intramuscular injection only as a booster vaccine has good safety and immunogenicity, and provides data support for the NEW CROWN vaccine booster strategy.