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▎The content team editor of WuXi AppTec.
On July 14, local time, the New England Journal of Medicine (NEJM) recently published an important new crown vaccine "mixed" study, adding new ideas to the immunogenicity and safety of mixed vaccination.
Evidence
.
This study from Umeå University in Sweden called CoVacc showed that after a shot of ChAdOx1n CoV-19 new crown vaccine, a second shot of mRNA-1273 induced higher antibody titers and neutralizing antibody titers , The protection against mutant strains in in vitro experiments is also stronger
.
Compared with the preliminary safety data of the Com-COV test and the immune response data of the CombiVacS test published by The Lancet, this Swedish study more intuitively compared the effects of the antibody of the same type and the two injections
.
Screenshot source: The New England Journal of Medicine This is a phase 4 study to explore the immunogenicity of the new crown vaccine and is still ongoing
.
The data in this report covered 88 medical staff who had received a ChAdOx1 nCoV-19 vaccine 9-12 weeks before the study
.
Among these subjects, 37 people chose the second dose of ChAdOx1 nCoV-19 (homologous booster), with a median age of 46 years (range 28-62 years); 51 people chose the second dose of mRNA- 1273 (heterologous booster immunization), the median age is 40 years (range 23-59 years)
.
On the day of the second vaccination, 7-10 days and 30 days after the vaccination, blood samples of the subjects were obtained to analyze the levels of new coronavirus-specific IgG antibodies and neutralizing antibodies
.
In addition, the subject also reported a reaction after the second shot
.
WuXi AppTec's content team mapped the new coronavirus spike protein (S) specificity and receptor binding domain (RBD) specific IgG in subjects in the ChAdOx1 nCoV-19 group and mixed group on the day of the second injection The antibody level is similar, and the neutralizing antibody level is also similar
.
7-10 days after the second shot of vaccination, the S-specific and RBD-specific IgG antibody levels in the subjects of the two shots of ChAdOx1 nCoV-19 group were 5 times that of the second shot of vaccination (P<0.
001); The levels of S-specific and RBD-specific IgG antibodies in group subjects were higher, reaching 115 times and 125 times that of the day of the second vaccination, respectively (P<0.
001)
.
Thirty days after the second vaccination, the levels of S-specific IgG antibodies in the two groups were still similar to the levels 7-10 days after the second vaccination
.
▲The level of S-specific (A) and RBD-specific (B) IgG antibodies in the two groups on the day of the second vaccination (P), 7-10 days and 30 days after vaccination
.
The rightmost control group is the data of 4 individuals who have been infected with the new crown and received a shot of ChAdOx1 nCoV-19 9-12 weeks before sampling
.
(Image source: Reference [1]) In the in vitro neutralization experiment against the original Swedish new coronavirus isolate (SARS-CoV-2/01/human/2020/SWE), it was observed by immunofluorescence analysis, The level of neutralizing antibodies in the mixed group was also higher
.
7-10 days after the second shot of vaccination, the serum neutralization titer (counted down to ID50) of the mixed group was 20 times that of the second shot of vaccination (P<0.
001); the serum neutralization of the two shots of ChAdOx1 nCoV-19 group The titer was only twice that of the second vaccination day (P=0.
09)
.
Compared with 7-10 days after the second shot of vaccination, one month after the second shot of vaccination, the neutralizing antibody titers of both groups increased by 1.
6-1.
7 times, but it was not obvious
.
At the same time, the research team also used the cytopathic effect assay to measure the serum antibodies of the two groups of subjects 7-10 days after the second inoculation against the original isolate and the B.
1.
351 mutant (Beta mutant, The neutralization effect was first confirmed in South Africa
.
This supports the finding that the level of neutralizing antibodies in the mixed group was higher
.
At the same time, it was also found that the antibodies of the mixed group had an in vitro neutralization effect on the B.
1.
351 mutant, while the antibodies induced by ChAdOx1 nCoV-19 both inoculated with both injections did not have a strong neutralization effect on the B.
1.
351 mutant
.
▲ two groups of neutralizing antibody in the subject
.
Figure A uses immunofluorescence analysis for the original isolate; Figure B uses the cytopathic effect determination for the original isolate and the B.
1.
351 mutant strain
.
(Image source: Reference [1]) From the point of view of reactogenicity, the subjects who received the second injection of mRNA-1273 reported more fever, headache, chills and muscle pain, but the degree of adverse reactions (mild, There was no significant difference in events between the two groups when grading (moderate, severe)
.
These adverse events are consistent with the safety observed in the previous studies with two injections of ChAdOx1 nCoV-19 or two injections of mRNA-127
.
Based on these data, the research team mentioned in the paper that mixing the mRNA-1273 vaccine 9-12 weeks after the initial ChAdOx1 nCoV-19 vaccine can effectively further stimulate the new coronavirus-specific B cell memory; moreover, the second shot Mixing the mRNA-1273 vaccine may provide better protection against the B.
1.
351 mutant strain
.
The editorial podcast published by NEJM at the same time carefully interpreted these findings
.
NEJM editor-in-chief Dr.
Eric Rubin mentioned that although mRNA vaccines have shown stronger immune responses as boosters in multiple studies, this study provides new evidence, but this study also has limitations.
It is only a small, in vitro study.
Not a randomized trial
.
Dr.
Lindsey Baden, deputy editor of NEJM's infectious disease field, emphasized that immune protection is affected by many factors.
Antibody level is an important indicator but not completely equivalent to protection
.
As for whether it will affect existing vaccination, Dr.
Lindsey Baden still recommends waiting for more scientific evidence to be published to better understand the impact of different vaccination strategies on different groups of people
.
On July 14, local time, the New England Journal of Medicine (NEJM) recently published an important new crown vaccine "mixed" study, adding new ideas to the immunogenicity and safety of mixed vaccination.
Evidence
.
This study from Umeå University in Sweden called CoVacc showed that after a shot of ChAdOx1n CoV-19 new crown vaccine, a second shot of mRNA-1273 induced higher antibody titers and neutralizing antibody titers , The protection against mutant strains in in vitro experiments is also stronger
.
Compared with the preliminary safety data of the Com-COV test and the immune response data of the CombiVacS test published by The Lancet, this Swedish study more intuitively compared the effects of the antibody of the same type and the two injections
.
Screenshot source: The New England Journal of Medicine This is a phase 4 study to explore the immunogenicity of the new crown vaccine and is still ongoing
.
The data in this report covered 88 medical staff who had received a ChAdOx1 nCoV-19 vaccine 9-12 weeks before the study
.
Among these subjects, 37 people chose the second dose of ChAdOx1 nCoV-19 (homologous booster), with a median age of 46 years (range 28-62 years); 51 people chose the second dose of mRNA- 1273 (heterologous booster immunization), the median age is 40 years (range 23-59 years)
.
On the day of the second vaccination, 7-10 days and 30 days after the vaccination, blood samples of the subjects were obtained to analyze the levels of new coronavirus-specific IgG antibodies and neutralizing antibodies
.
In addition, the subject also reported a reaction after the second shot
.
WuXi AppTec's content team mapped the new coronavirus spike protein (S) specificity and receptor binding domain (RBD) specific IgG in subjects in the ChAdOx1 nCoV-19 group and mixed group on the day of the second injection The antibody level is similar, and the neutralizing antibody level is also similar
.
7-10 days after the second shot of vaccination, the S-specific and RBD-specific IgG antibody levels in the subjects of the two shots of ChAdOx1 nCoV-19 group were 5 times that of the second shot of vaccination (P<0.
001); The levels of S-specific and RBD-specific IgG antibodies in group subjects were higher, reaching 115 times and 125 times that of the day of the second vaccination, respectively (P<0.
001)
.
Thirty days after the second vaccination, the levels of S-specific IgG antibodies in the two groups were still similar to the levels 7-10 days after the second vaccination
.
▲The level of S-specific (A) and RBD-specific (B) IgG antibodies in the two groups on the day of the second vaccination (P), 7-10 days and 30 days after vaccination
.
The rightmost control group is the data of 4 individuals who have been infected with the new crown and received a shot of ChAdOx1 nCoV-19 9-12 weeks before sampling
.
(Image source: Reference [1]) In the in vitro neutralization experiment against the original Swedish new coronavirus isolate (SARS-CoV-2/01/human/2020/SWE), it was observed by immunofluorescence analysis, The level of neutralizing antibodies in the mixed group was also higher
.
7-10 days after the second shot of vaccination, the serum neutralization titer (counted down to ID50) of the mixed group was 20 times that of the second shot of vaccination (P<0.
001); the serum neutralization of the two shots of ChAdOx1 nCoV-19 group The titer was only twice that of the second vaccination day (P=0.
09)
.
Compared with 7-10 days after the second shot of vaccination, one month after the second shot of vaccination, the neutralizing antibody titers of both groups increased by 1.
6-1.
7 times, but it was not obvious
.
At the same time, the research team also used the cytopathic effect assay to measure the serum antibodies of the two groups of subjects 7-10 days after the second inoculation against the original isolate and the B.
1.
351 mutant (Beta mutant, The neutralization effect was first confirmed in South Africa
.
This supports the finding that the level of neutralizing antibodies in the mixed group was higher
.
At the same time, it was also found that the antibodies of the mixed group had an in vitro neutralization effect on the B.
1.
351 mutant, while the antibodies induced by ChAdOx1 nCoV-19 both inoculated with both injections did not have a strong neutralization effect on the B.
1.
351 mutant
.
▲ two groups of neutralizing antibody in the subject
.
Figure A uses immunofluorescence analysis for the original isolate; Figure B uses the cytopathic effect determination for the original isolate and the B.
1.
351 mutant strain
.
(Image source: Reference [1]) From the point of view of reactogenicity, the subjects who received the second injection of mRNA-1273 reported more fever, headache, chills and muscle pain, but the degree of adverse reactions (mild, There was no significant difference in events between the two groups when grading (moderate, severe)
.
These adverse events are consistent with the safety observed in the previous studies with two injections of ChAdOx1 nCoV-19 or two injections of mRNA-127
.
Based on these data, the research team mentioned in the paper that mixing the mRNA-1273 vaccine 9-12 weeks after the initial ChAdOx1 nCoV-19 vaccine can effectively further stimulate the new coronavirus-specific B cell memory; moreover, the second shot Mixing the mRNA-1273 vaccine may provide better protection against the B.
1.
351 mutant strain
.
The editorial podcast published by NEJM at the same time carefully interpreted these findings
.
NEJM editor-in-chief Dr.
Eric Rubin mentioned that although mRNA vaccines have shown stronger immune responses as boosters in multiple studies, this study provides new evidence, but this study also has limitations.
It is only a small, in vitro study.
Not a randomized trial
.
Dr.
Lindsey Baden, deputy editor of NEJM's infectious disease field, emphasized that immune protection is affected by many factors.
Antibody level is an important indicator but not completely equivalent to protection
.
As for whether it will affect existing vaccination, Dr.
Lindsey Baden still recommends waiting for more scientific evidence to be published to better understand the impact of different vaccination strategies on different groups of people
.
