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cdc.gov/coronavirusInfection -induced and hybrid immunity
Jefferson Jones, MD MPH FAAP
CDR, US Public Health Service
Shifts in vaccine -induced, infection -induced, and hybrid immunity against SARS -CoV-2
among blood donors aged ≥16 years —United States, Quarter 2 2021 –Quarter 3 2022
No infection or vaccination
Vaccine only -induced
antibodies
Infection only -induced
antibodies
Both infection and
vaccination -induced
antibodies (hybrid immunity)
Jones MMWR 2023: Data from a longitudinal, national cohort of
>70,000 blood donors. Vaccine history is from self report. Infection
history is based on presence of anti -nucleocapsid antibodies.
Shifts in vaccine -induced, infection -induced, and hybrid immunity against SARS -CoV-
2 among people aged ≥16 years by age group —United States, Q2 2021 –Q3 2022
No infection or vaccination
Vaccination without previous
infection
Previous infection without
vaccination
Both previous infection and
vaccination (hybrid
immunity)
16–29 years 30–49 years30–49 years
50–64 years ≥65 years
Jones MMWR 2023: Data from a longitudinal, national
cohort of >70,000 blood donors. Vaccine history is from
self report. Infection history is based on presence of anti-
nucleocapsid antibodies.
Quantitative anti -spike antibody titers by age group
and by infection and vaccine status, Jul -Oct 2022
Previous infection,
unvaccinatedPrevious infection,
vaccinatedVaccinated, no previous
infection
Spike antibody titers (BAU/ml)
16–29 30 –49 50 –64 ≥65
Age (years)
Source: CDC (unpublished). Data from nationwide blood donor cohort
Vaccine history is from self report. Infection history is based on presence of anti -nucleocapsid antibodies. N=2,553 N=15,437 N=27,130 N=26,034 N=3,711 N=44,486 N=21,281
63828993
0102030405060708090100
Mar-Apr May-Jun Jul-Aug Sep-Oct Nov-DecSeroprevalence (%)
Month7585929799
0102030405060708090100
Mar-Apr May-Jun Jul-Aug Sep-Oct Nov-DecSeroprevalence (%)
MonthPediatric infection -induced and combined (vaccine -and infection -induced)
Seroprevalence from U.S. commercial laboratories —March –December 2022
Source: https://covid.cdc.gov/covid -data -tracker/#pediatric -seroprevalence and unpublished data (CDC) Data from repeat, cross -sectional study on blood specimens collected by
commercial laboratories. Vaccine history is unknown in this study. Infection -induced seroprevalence estimated from blood specime ns tested for anti -nucleocapsid antibodies:
the number of specimens per 2 -month collection period were, by age group: 6 –11 months: 157; 12 –23 months: 724; 2 –4 years: 2,165; 5–11 years: 9,247; and 12 –17 years: 14,570.
Combined (vaccine -and infection -induced seroprevalence estimated from specimens tested for both spike and nucleocapsid antibodi es: >99% of samples tested for anti -
nucleocapsid antibodies were tested for anti -spike antibodies. 5Infection -induced Combined (vaccine -and infection -induced)
Antibody titers depend more on history of infection and
vaccination than age
6–23 month 2 –4 yrs 5– 11 yrs 12–17 yrs
Age group 10000
1000
100
10Spike antibody titers (BAU/ml)N=612 N=1,769 N=13,785 N=8,299Spike antibody titers (BAU/ml)
Previous infection,
unvaccinatedPrevious infection,
vaccinatedVaccinated, no
previous infection
*Does not include specimens with no detectable antibodies
Source: CDC (unpublished)National blood donor seroprevalence study
Ages ≥16 years, Jul –Oct 2022National pediatric commercial lab seroprevalence study
Ages 6 months –17 years, Nov –Dec 2022, among
specimens with antibodies*N=3,711 N=44,486 N=21,281
RBD Ab levels by history of infection and vaccination
status— children 6 mo—17+ yrs, PROTECT study
0.000.010.020.03RBD AUC6 months — 17+ years
1 infection only n=175
2 infections only n=201 dose only n=36
1 dose + infection only n=22
mRNA primary series only n=306
mRNA primary series + ³1 infection only n=251
Booster* only n=47
Booster+ ³1 infection only n=125
Antigen exposures
Blood draw within 6 months of immune modifying event, time between immune modifying events is <365 days.
RDB AUC: area under the curve of receptor -binding domain antibodies, a quantitative measure of binding antibodies.
*Booster Bivalent and monovalent boosters grouped together.
Lyski, Z and Porter, C. Unpublished data from the PROTECT cohort. PROTECT protocol: https://www.ncbi.nlm.nih.gov/pmc/articles /PM C9377426/
RBD Ab levels by history of infection and vaccination status
by age group —children 6 mo—17+ yrs, PROTECT study
Immune -modifying events (in any order)
0.000.010.020.03RBD AUC6 months — <5 years
1 Infection only n=33
2 infections only n=61 Dose+ infection only n=4
mRNA primary series only n=13
mRNA primary series + ³1 infection only n=17
Booster+ infection n=1
Antigen exposures1 dose only n=1
Booster* only n=1
0.000.010.020.03RBD AUC6 months — <5 years
1 Infection only n=33
2 infections only n=61 Dose+ infection only n=4
mRNA primary series only n=13
mRNA primary series + ³1 infection only n=17
Booster+ infection n=1
Antigen exposures1 dose only n=1
Booster* only n=1
0.000.010.020.0312-17+RBD AUC
Antigen exposures1 infection only n=41
2 infections only n=91 dose only n=12
1 dose + infection only n=5
mRNA primary series only n=125
mRNA primary series + ³ 1infection only n=64
Booster* only n=16
Booster*+ ³ 1 infection only n=65
0.000.010.020.0312-17+RBD AUC
Antigen exposures1 infection only n=41
2 infections only n=91 dose only n=12
1 dose + infection only n=5
mRNA primary series only n=125
mRNA primary series + ³ 1infection only n=64
Booster* only n=16
Booster*+ ³ 1 infection only n=65
0.000.010.020.03RBD AUC5-11
1 infection only n=71
dose 1 only n=23
1 dose + infection only n=15
mRNA primary series only n=169
mRNA primary series + ³1 infection only n=172
Monovalent booster only n=31
Booster+ infection ³1 infection only n=61
Antigen exposures2 infections only n=10
0.000.010.020.03RBD AUC5-11
1 infection only n=71
dose 1 only n=23
1 dose + infection only n=15
mRNA primary series only n=169
mRNA primary series + ³1 infection only n=172
Monovalent booster only n=31
Booster+ infection ³1 infection only n=61
Antigen exposures2 infections only n=10n= 72 n= 552 n= 337
SARS -CoV-2 neutralizing antibody ( nAb) studies
▪In unvaccinated persons, infection -induced nAb titers highest against variants
similar to the variant that infected the person1
▪nAb titers in people with hybrid immunity may wane slower than in
people vaccinated without infection2
–Infection after vaccination may be moderated by imprinting3
▪Omicron
–Omicron variants demonstrate greater escape from neutralization than older
variants1–2,4–6
–Additional vaccine doses beyond primary series increase Omicron nAb titers4,5
–Hybrid immunity results in higher Omicron nAb titers than immunity from
infection or vaccination alone, including to recent Omicron subvariants4
1 Rössler 2022 NEJM ; 2 Qu 2022 NEJM ; 3 Wheatley Trends Immunol 2021 ; 4 Kurhade 2023 Nat Med ;
5 Gaebler 2022 OFID ; 6 Barateau 2023 Sci Transl Med
Other SARS -CoV-2 immunity laboratory study highlights
▪Hybrid immunity appears to result in stronger more robust immune response
using other measures as well, including
–
–
–Infection -induced and hybrid immunity result in higher IgA titers than
vaccine -induced immunity1,2
Hybrid immunity may result in higher proportion of anti -spike memory
B cells than vaccination alone3
Hybrid immunity induces T cells and antibodies directed against non -
spike viral antigens4
▪T-cell immunity from both infection and vaccination well preserved against
Omicron4
–Cellular immunity likely important in preventing severe disease5
1 Barateau 2023 Sci Transl Med ; 2 Sheikh -Mohamed Immunol Rev 2022 ;
3 Bednarski 2022 mBio ; 4 Naranbhai 2022 Cell ; 5 Moss 2022 Nature
Systematic review of protection against Omicron from infection, hybrid with
monovalent primary series, and hybrid with first monovalent booster
Bobrovitz 2023 Lancet
Conclusions
▪SARS -CoV-2 infection can cause severe disease, death, and long -term morbidity, whereas COVID -19
vaccination is safe and effective at preventing severe COVID -19 disease
▪The proportion of people with immunity from infection or hybrid immunity has increased
▪Immunity following vaccination and infection wanes over time, and both monovalent primary series
vaccination and history of pre -Omicron infection provided much lower protection during Omicron than
during prior COVID -19 waves
▪Compared with protection from infection or vaccination alone, hybrid immunity likely better protects
against infection and severe disease with Omicron
▪Stronger protection is likely provided when the infecting variant is similar to the circulating variant, but this
may be complicated by imprinting
▪Current protection likely influenced by both cumulative number of vaccine doses, number of times
infected, and timing of most recent vaccination or infection, and how closely the circulating variant
matches the vaccine or prior infection
▪Conclusions apply to both children and adults
Acknowledgments
▪Tarayn Fairlie
▪Melissa Briggs -Hagen
▪Melissa Coughlin
▪Natalie Thornburg
▪Claire Midgley▪Ian Plumb
▪Amadea Britton
▪Ruth Link -Gelles
▪Amanda Payne
▪PROTECT team
For more information, contact CDC
1-800-CDC-INFO (232-4636)
TTY: 1- 888- 232-6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the
official position of the Centers for Disease Control and Prevention.