Chen Wei and other experts: Adenovirus vector vaccine is strengthened better

What is the explanation for the decrease in the protection of inactivated vaccines? Chen Wei and others: Adenovirus vector vaccine is better strengthened

What is the explanation for the decrease in the protection of inactivated vaccines? Chen Wei et al.

Mass vaccination of an effective COVID-19 vaccine is considered a key measure to control the pandemic
.

However, with the continuous development of the epidemic, the protection time of vaccinations and the more threatening virus variants have all put forward new challenges to the prevention and control of the epidemic

On September 6, researchers from Jiangsu Provincial Center for Disease Control and Prevention, Beijing Institute of Biotechnology, CanSino and other teams published a study on the preprint platform medRvix, titled "Kexing Inactivated Vaccine CoronaVac "Heterologous prime-boost immunization with CoronaVac and Convidecia" ("Heterologous prime-boost immunization with CoronaVac and Convidecia")
.

The corresponding authors of the study are Academician Chen Wei of the Academy of Military Medicine of the Academy of Military Sciences and Zhu Fengcai, deputy director of the Jiangsu Provincial Center for Disease Control and Prevention

Regarding sequential vaccination, at the State Council Joint Prevention and Control Mechanism press conference held on September 7, Zheng Zhongwei, the leader of the vaccine research and development team of the scientific research team and director of the Science and Technology Development Center of the National Health Commission, introduced that the vaccine research and development team is in Prior to this, an expert discussion meeting was organized on August 2, and the experts clearly recommended support for sequential immunization research and pilot work
.

He also emphasized that at present, some R&D institutions in China are also carrying out related sequential immunization research work at home and abroad.
Only after obtaining sufficient scientific data on safety and immunogenicity or effectiveness, can we evaluate the Sequential immunization work for large-scale populations provides expert advice
.

Chen Wei and others mentioned in this paper that in animal experiments, the immunogenicity of the new crown vaccine of different technical routes is better than that of the same vaccine
.

They believe that, theoretically, the sequential immunization plan can promote the maturation of antibody affinity and affect the breadth of immunity by introducing different antigens, carrier types, delivery routes, doses or adjuvants at different times

Up to now, after basic immunization, there are dozens of ongoing sequential intensive needle studies
.

However, this study is the first to report the sequential primary immunization of SARS-CoV-2 inactivated vaccine (CoronaVac) and recombinant adenovirus type 5 vector vaccine (Convidecia)-booster immunization in China 18-59 years old Safety and immunogenicity in adults

It is worth mentioning that 11.
8%-27.
1% of participants who completed 2 vaccinations 3-6 months before this study had SARS-CoV-2 neutralizing antibodies positive; 1-2 before the study Among those who completed one vaccination every month, 4.
0%-5.
9% of participants had positive SARS-CoV-2 neutralizing antibodies in their serum
.

The paper mentioned that these studies have shown that humoral immunity will be significantly weakened over time and may lose protection, especially when the new coronavirus variant is dominant

Overall, in terms of safety, participants in the adenoviral vector vaccine reported more adverse reactions than inactivated vaccines in the two-dose and three-dose schedule cohorts
.

In the two-dose schedule cohort, participants who received the second dose of adenovirus vector vaccine reported a higher incidence of injection site reactions than participants who received the same inactivated vaccine
.

However, the reported rates of systemic reactions were similar between the two groups

However, the severity of the injection site and systemic reactions is generally mild to moderate and usually disappears within 1 or 2 days
.

Pain at the injection site is the most common injection site reaction, and fever and fatigue are the most common systemic reactions

In terms of immunogenicity, the data showed that in the three-dose and two-dose cohorts, significant reactions were observed after booster vaccination
.

In the three-dose vaccination group, the neutralizing antibody GMTs before the booster vaccination were 2.
5 (2.
3, 2.
7) and 2.
2 (2.
1, 2.
3) on day 0, respectively.
After a booster dose of adenovirus vector vaccine, they were neutralized 14 days later.
The antibody GMTs was 197.
4 (167.
7, 232.
4), and the antibody level increased by about 78 times; after another boost of inactivated vaccine, the neutralizing antibody GMTs was 33.
6 (28.
3, 39.
8), which was about 15.
2 times higher
.

The research team said that the data showed that the level of neutralizing antibody growth after sequential strengthening was significantly better than the effect of homologous strengthening
.

In the two-dose vaccination group, the neutralizing antibody GMTs before the booster vaccination were 2.
1 (2.
0, 2.
3) and 2.
1 (2.
0, 2.
1) on day 0, respectively.
After another dose of adenovirus vector vaccine boosted, the neutralizing antibody GMTs It was 54.
4 (37.
9, 78), and the antibody level increased by at least 25.
7 times; after another dose of inactivated vaccine was boosted, the neutralizing antibody GMTs was 12.
8 (9.
3, 17.
5), and the antibody level increased by 6.
2 times
.

The research team believes that the increase in immunogenicity may be related to the activation of different natural immune responses by inactivated vaccines and adenovirus vector vaccines
.

The research team also mentioned that on the 28th day after the booster injection, the average neutralizing antibody level decreased, but the neutralizing antibody GMTs of the sequential immunization group was still significantly higher than that of the homologous booster group (150.
3 [128.
6 in the three-dose vaccination group] ,175.
7] vs.
35.
3 [29.
4, 42.
4]; 49.
6 [35.
1, 70.
2] vs.
10.
6 [8.
3, 13.
5] in the two-dose vaccination group
.

RBD-specific ELISA antibody response comparison
.

The study also showed that according to the neutralizing antibody titer, both sequential and homologous enhancement can induce a significant immune memory response, and the binding of RBD to IgG is significantly enhanced
.
However, the adenovirus vector vaccine boost induced the level of RBD-binding IgG GMTs higher than that of the homologous boost
.
The study also mentioned that whether it is the sequential immune group or the homologous immune group, the main binding antibody response is related to IgG1
.

The research team concluded that the results of this study show that for healthy adults 18-59 years old, the sequential primary immunization-enhancement regimen is safe and highly immunogenic
.
Compared with the same kind of booster vaccine using the inactivated vaccine, the humoral response and Th1 cell immune response of the adenovirus vector vaccine after booster immunization are stronger
.

This means that based on the assumption that the level of neutralizing antibody is related to the level of protection, the sequential primary immunization-boost immunization program with adenovirus vector vaccine and inactivated vaccine has better protection
.
This research may help implement a booster strategy for people who have previously received two doses of inactivated vaccine
.

In fact, according to the information on the ClinicalTrials.
gov website, Cansino launched two studies on May 19, 2021 and July 7, 2021 to evaluate adenovirus vector vaccines in China between 18-59 and 60-year-olds.
Sequential vaccination effect of two age groups and above
.
The paper released this time also mentioned that in addition to this latest study, they are also conducting another study to evaluate the use of inactivated vaccines and adenovirus vector vaccines in the elderly population for sequential primary-booster immunization
.

Focus on the new crown pneumonia epidemic