Phase 1 clinical results of nebulized new crown vaccine published "The Lancet-Infectious Diseases"

More than 20 intramuscular COVID-19 vaccines have been approved for use worldwide
.

In order to provide more options for vaccines and vaccination methods, a number of candidate vaccines that are expected to solve the "pain" of "injection" are also being developed, including oral vaccines and vaccines for nasal administration

Today, the initial report of the Phase 1 clinical trial of the new crown vaccine (Ad5-nCoV) of adenovirus vector type 5 (Ad5-nCoV) developed by the team of Academician Chen Wei of the Chinese Academy of Engineering and CanSino Biologics "Sciology" was published
.

This research was carried out at Zhongnan Hospital of Wuhan University

The results of the study showed that Ad5-nCoV was well tolerated by nebulized inhalation and did not cause any serious adverse events related to the vaccine
.

One dose of aerosolized Ad5-nCoV is equivalent to one-fifth of the dose of a single intramuscular injection.

The Ad5-nCoV vaccine uses the Ad5 adenovirus vector to express the spike (S) protein of the new coronavirus
.

Previously, the Ad5-nCoV vaccine (Kewisha) administered intramuscularly had been approved by the China National Medical Products Administration for conditional marketing.

This randomized, open phase 1 clinical trial aims to evaluate the safety and immunogenicity of nebulized Ad5-nCoV vaccine in Chinese healthy adults (≥18 years of age).
The study excluded breastfeeding women, pregnant women, and severe cases.
People with chronic diseases or allergies
.

From September 28th to September 30th, 2020, 130 subjects were recruited and randomly assigned 1:1:1:1:1 into 5 groups (26 people in each group), respectively, through intramuscular injection and nebulization inhalation Or mixed vaccination with Ad5-nCoV
.

Subjects in the two aerosol inhalation groups were vaccinated with two high-dose (both 2×1010 virus particles) or low-dose (both 1×1010 virus particles) Ad5-nCoV at 28 days intervals; mixed The immunization group received intramuscular injection (5×1010 virus particles) on day 0 and nebulized inhalation (2×1010 virus particles) Ad5-nCoV on day 28; intramuscular injection group received a single dose (5×1010 virus particles) on day 0 or Two doses (two doses total of 10×1010 virus particles) Ad5-nCoV
.

The paper pointed out that the inhalation dose of a single dose is equivalent to one-fifth or two-fifths of the usual single-dose intramuscular injection
.

For the main safety study endpoint, there was no significant difference in the incidence of any adverse events within 7 days after the first vaccination or booster vaccination for different vaccination routes
.

The incidence of adverse events in each group is as follows: 18 people (69%) in the two-dose high-dose aerosol inhalation group, 19 people (73%) in the two-dose low-dose aerosol inhalation group, 19 people (73%) in the mixed immunization group, single-dose There were 19 people (73%) in the intramuscular injection group and 15 people (58%) in the two-dose intramuscular injection group

The main adverse events within 7 days after the first vaccination and booster immunization were fever (62/130, 48%), fatigue (40/130, 31%) and headache (46/130, 35%)
.

Within 7 days of the first vaccination, the nebulization inhalation group (13/52, 25%) had fewer adverse events than the intramuscular injection group (including the mixed immunization group) (49/78, 63%)
.

No serious adverse events were found within 56 days after the first vaccination

▲Adverse events reported in each group within 7 days of the first dose (A) and booster vaccination (B)
.

Two doses of high-dose aerosol inhalation-HDmu, two doses of low-dose aerosol inhalation-LDmu, mixed immunity-MIX, a single dose of intramuscular injection of -1 Dim, and two doses of intramuscular injection of -2 Dim a day

In terms of the main immunogenicity research endpoint, 28 days after the last vaccination, although the concentrations of IgG and IgA antibodies specific to the new coronavirus S protein receptor binding domain (RBD) in two aerosol inhalations were lower than the corresponding antibody concentrations in one injection, However, the neutralizing antibody titers of the nebulized inhalation group were similar to those of the patients receiving intramuscular injection
.

The paper pointed out that in this test, there is a moderate correlation between RBD-specific IgG antibody titers and neutralizing antibody titers
.

Neocorona neutralizing antibodies are not only derived from RBD-related antibodies, but also from N-terminal domain-related antibodies of S protein, which may partly explain the difference in seroconversion rates between RBD-specific IgG antibodies and neutralizing antibodies

The geometric mean titers of neutralizing antibodies against the new coronavirus and the geometric mean concentrations of RBD-specific IgG antibodies and IgA antibodies induced by each group were:

Two-dose high-dose aerosol inhalation group: 107,261 EU/mL, 312 EU/mL; Two-dose low-dose aerosol inhalation group: 105,289 EU/mL, 297 EU/mL; Mixed immunization group: 396, 2013 EU /mL, 777 EU/mL; single-dose intramuscular injection: 95,915 EU/mL, 425 EU/mL; two-dose intramuscular injection group a day: 180, 1190 EU/mL, 521 EU/mL
.

▲After vaccinating Ad5-nCoV vaccine by different routes, the concentration of IgG antibody (A) and IgA antibody (B), and the level of neutralizing antibody (C) were measured
.
Two doses of high-dose aerosol inhalation-HDmu, two doses of low-dose aerosol inhalation-LDmu, mixed immunity-MIX, a single dose of intramuscular injection of -1 Dim, and two doses of intramuscular injection of -2 Dim a day
.
(Image source: Reference [1])

Based on these data, the paper points out that the nebulized Ad5-nCoV vaccine is well tolerated, and compared with intramuscular injection of the vaccine, it induces similar humoral and cellular immune responses, which is valuable for epidemic prevention and control.
The effectiveness and cost-effectiveness of aerosol inhalation vaccination should be further evaluated in the research
.

Reference

[1] Shipo Wu, et al.
, (2021).
Safety, tolerability, and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV)in adults: preliminary report of an open-label and randomised phase 1 clinical trial.
The Lancet Infectious Diseases, DOI: https://doi.
org/10.
1016/S1473-3099(21)00396-0

[2] Cansinotech.
Retrieved July 27, 2021, from http://