Immunogenicity of BNT162b2 in children 6 months to under 5 years of age with previous SARS-CoV-2 infection, in the era of Omicron predominance

Abstract

Background: Children 6 months to < 5 years old are recommended to receive 3-dose regimen of BNT162b2. Children previously infected with Omicron variant of SARS-CoV-2 develop immunity from natural infection, therefore may require fewer doses of vaccine.

Objective: To compare immunogenicity of 1- or 2-dose BNT162b2 in healthy children post COVID-19 with 3-dose BNT162b2 in COVID-naïve children.

Methods: Children aged 6 months to < 5 years who developed COVID-19 during the Omicron-predominant period were enrolled; Group A 3-6 months(N = 40) and Group B > 6 months(N = 40) prior to vaccination. Participants in Group A and B received 2-dose BNT162b2 intramuscularly 1 month apart. COVID-naïve children were enrolled as a control group (N = 40) and received 3-dose BNT162b2 at month 0,1,3. Neutralizing antibody against Omicron variant(BA.2.75 and BA.4/5) was determined by pseudovirus assays(pVNT) as reported by neutralization dilution for 50%inhibition (ID₅₀) at 28 days after the 1^st and 2^nd dose.

Results: From October-November 2022, 120 children with a median age of 2.8 years (IQR 1.6-4.0) were enrolled. The median duration since COVID-19 to vaccination was 4.4 months(IQR 3.8-5.4) in Group A and 7.9 months(7.0-8.5) in Group B. In Group A, the geometric means(GMs) of pVNT-BA.2.75 ID₅₀ were 553 (95%CI 338-906) and 753(516-1098) after 1 and 2 doses, respectively, and the GMs of pVNT-BA.4/5 ID₅₀ were 1936(1402-2673) and 1885(1414-2512), respectively. In Group B, the GMs of pVNT-BA.2.75 ID₅₀ were 1383(1100-1742) and 1419 (1104-1823), and the GMs of pVNT-BA.4/5 ID₅₀ were 2627(2048-3367) and 2056(1546-2735), respectively. Meanwhile in COVID-naïve group, the GMs of pVNT-BA.2.75 and pVNT-BA.4/5 ID₅₀ were 158(98-255) and 59(31-114) after the 3^rd dose, respectively. The geometric mean ratio(GMR) of pVNT-BA.2.75 ID₅₀ after 1 dose in Group A and B compared with after 3 doses in COVID-naïve group were 3.50 (1.93-6.34) and 8.74 (4.79-15.95), respectively. The GMR of pVNT-BA.2.75 ID₅₀ after 1 dose in Group B compared with Group A was 2.50 (1.45-4.31).

Conclusions: Children previously infected with SARS-CoV-2 Omicron variant, developed robust neutralizing antibody response against Omicron variant after single-dose BNT162b2. Children with an interval of > 6 months since COVID-19 infection developed higher neutralizing antibody response compared to those with a 3-to-6-month interval.

Keywords: Anti-SARS-CoV-2 IgG; BNT162b2 vaccine; Child; Infant; Neutralizing antibody titer; SARS-CoV-2 vaccine.

Fig. 1

Flow diagram of study participants included in immunogenicity analyses.

Fig. 2

Geometric means (95% CI) of pVNT (ID₅₀) after BNT162b2 vaccination in healthy children 6 months to under 5 years of age with history of COVID-19 during Omicron-predominant period and in children without history of COVID-19, (A) pVNT-BA.2.75 and (B) pVNT-BA.4/5. *p < 0.05; **p < 0.01; ***p < 0.001 by two-independent sample t-test.Group A: Past COVID-19 for 3–6 months; Group B: Past COVID-19 for > 6 months; ID₅₀: Neutralization dilution for 50% pseudovirus inhibition; pVNT-BA.2.75: Pseudovirus neutralization test against SARS-CoV-2 Omicron sublineage BA.2.75; pVNT-BA.4/5: Pseudovirus neutralization test against SARS-CoV-2 Omicron sublineage BA.4/5.

Fig. 3

Geometric means (95% CI) of sVNT-BA.4/5 (%inhibition) after BNT162b2 vaccination in healthy children 6 months to under 5 years of age with history of COVID-19 during Omicron-predominant period and in children without history of COVID-19. ***p < 0.001 by two-independent sample t-test. Group A: Past COVID-19 for 3–6 months; Group B: Past COVID-19 for > 6 months; sVNT-BA.4/5: Surrogate virus neutralization test against SARS-CoV-2 Omicron sublineage BA.4/5.