Reduced neutralization against Omicron variant in fully immunized adolescents with BNT162b2 vaccine

As of January 27, 2022, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 366 million worldwide and caused over 5.6 million deaths. Several reports confirm that those over the age of 65 are at a greater risk of SARS-CoV-2 infections.

Study: Loss of Pfizer (BNT162b2) Vaccine-Induced Antibody Responses against the SARS-CoV-2 2 Omicron Variant in Adolescents and Adults. Image Credit: OSORIOartist / Shutterstock.com

Background

Despite the lower number of cases, children can still contract SARS-CoV-2 and develop symptoms, as well as spread the virus to others. In fact, some children may even develop severe symptoms of the coronavirus disease 2019 (COVID-19), which can include a life-threatening complication known as a multisystem inflammatory syndrome in children (MIS-C), that may necessitate hospitalization.

The Pfizer-BioNTech BNT162b2 COVID-19 vaccine is a lipid nanoparticle-based messenger ribonucleic acid (mRNA) vaccine that encodes for the full-length SARS-COV-2 spike protein. This vaccine is administered to adults at a dose of 30-µg/dose with a 21-day interval.

Today, the United States Food and Drug Administration (FDA) has approved the use of the Pfizer-BioNTech COVID-19 vaccine for all individuals over the age of five. Since new viral variants of concern (VOCs) continue to arise, vaccine immunogenicity and efficacy must be evaluated on a regular basis.

As compared to the original wildtype SARS-CoV-2 strain and other VOCs, new investigations with both COVID-19 patients and completely BNT162b2 vaccinated individuals demonstrate much lower neutralizing titers against the developing Omicron variant. Previously SARS-CoV-2 infected vaccinees showed increased neutralizing titers against the Omicron variant after receiving a third booster dose of the BNT162b2 at six months.

In a recent Lancet* preprint, researchers compared the humoral immune response in adolescents and adults after being completely immunized with the Pfizer BNT162b2 vaccine, as well as their binding and neutralization titers against the Wuhan strain and circulating VOCs, including the recently discovered Omicron variant.

Study findings

As compared to adults, adolescents had considerably higher immunoglobulin G (IgG) binding titers for the full-length spike protein, the S1 receptor-binding domain (RBD), and the N Terminal Domain (NTD). The median spike IgG binding titers in adolescents were 388,975 AU/mL, while the median in adults was 182,997 AU/mL.

The difference in S-1 RBD binding titers between teenagers, who had a median level of 187,034 AU/mL, and adults were similar. The antibody binding titers for the NTD domain were 6,946 AU/mL in adolescents and 2,868 AU/mL in adults.

Adolescents had a greater spike IgA and RBD binding titers than adults; however, no difference in IgM binding titers at one-month post-immunization was observed when compared to adults.

Importantly, the scientists found no change in antibody binding titers against seasonal beta coronaviruses like HCoV-HKU1 and HCoV-OC43 between adolescents and adults for all studied antibody isotypes. However, these titers were greater than pre-pandemic healthy control levels for all antibody isotypes tested. Taken together, it does not appear that the larger vaccine-induced antibody response in teenagers is attributable to pre-existing immunity to seasonal coronavirus, which has been previously suggested.

The authors also tested the vaccine samples against SARS-CoV-2 Beta (B.1.351), Delta (B.1.617.2), Gamma (P.1), and Mu variants to determine whether there were any functional variations in the antibody repertoire or the capacity to bind and neutralize viral VOCs (B.1.621). All vaccinated plasma samples had antibody binding for RBD and spike, as well as neutralization titers for all examined variants.

Adolescents and adults exhibited a two to three-fold drop in binding against the Beta and Mu variants and a 1.5- to two-fold decline against the Delta and Gamma versions in spike IgG binding titers. While there was a 1.5- to two-fold reduction in binding against the Beta variant, no difference was observed between the Delta and Gamma variants.

Furthermore, a three to five-fold reduction in titers against the Beta variant and a 1.8- to two-fold decline against the Mu variant were observed in terms of viral neutralization. Adult samples exhibited minor changes against the Gamma and Delta variants, as previously described. Overall, the teenage and adult samples had similar levels of binding and neutralization.

The recent emergence of the SARS-CoV-2 Omicron variant, as well as its rapid dissemination around the world, has raised serious doubts about the potential of vaccine-induced immunity to neutralize this new viral strain. Adolescents, like adults, have significantly lower RBD binding IgG titers against the Omicron (B.1.1.529) variant than the WT RBD, as measured by enzyme-linked immunosorbent assay (ELISA).

In both adults and adolescents, the reduction is three to four times. Adolescent vaccinees had a median IgG binding titer of 10,038 AU/mL, while Omicron vaccinees had a titer of 3,340 AU/mL. The median binding titer in adults was 6,252 AU/mL, while that against the Omicron variant was 1,787 AU/mL. Adolescent vaccine recipients also struggled to neutralize the Omicron variant, with only three of the 15 adolescents and one of the 18 adults showing measurable titers.

Implications

At one month after receiving the Pfizer vaccine, adolescent vaccine recipients had considerably stronger binding and neutralizing antibody responses to SARS-CoV-2, with approximately comparable breadth against VOCs. The investigators also discovered that the Omicron variant significantly reduced the neutralizing activity of mRNA vaccine-induced responses in both adults and adolescents, with the great majority of donors displaying no detectable neutralizing activity.

Taken together, these data imply that a two-dose BNTb162b vaccine series may not be sufficient to protect against the Omicron variant and that booster vaccination in teenagers is necessary.

*Important notice

This study is a preliminary scientific report that has not yet been peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Colin Lightfoot

Colin graduated from the University of Chester with a B.Sc. in Biomedical Science in 2020. Since completing his undergraduate degree, he worked for NHS England as an Associate Practitioner, responsible for testing inpatients for COVID-19 on admission.