A recent study under review on the Journal of Clinical Immunology and currently available on the preprint server Research Square* analyzes the contribution of antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor binding domain (RBD) in vaccinated adults and kids, in addition to individuals who’re naturally infected by SARS-CoV-2 variants.

Study: Infection and vaccine induced Spike antibody responses against SARS-CoV-2 Variants of concern in immune naïve children and adults. Image Credit: Yurii_Yarema / Shutterstock.com

SARS-CoV-2 infection in adults and kids

In keeping with the World Health Organization (WHO), the survival of emergent SARS-CoV-2 variants of interest (VOIs) and variants of concern (VOCs) relies on viral infectivity, immune evasion, and transmissibility. These viral characteristics are different amongst VOIs and VOCs, which could be resulting from specific mutations across the spike protein.

Examination of antibody responses against viral variants will help elucidate the effect of mutations throughout the spike protein, in addition to in epistasis, where mutations of 1 site affect other mutations. Nonetheless, information on SARS-CoV-2 humoral immunogenicity, in addition to protection against emerging variants in children is proscribed.

Differences between the innate and adaptive immune systems in adults and kids result in different immune responses following SARS-CoV-2 infection. For instance, several studies have reported different adaptive humoral responses in children as in comparison with adults. To this end, higher antibody titers and neutralization to VOCs in children have been reported by some, while others have reported higher antibody titers but similar neutralization as in comparison with adults.

Overall, the lower prevalence of the coronavirus disease 2019 (COVID-19) in children prior to the emergence of the SARS-CoV-2 Omicron VOC could be resulting from higher asymptomatic infections on this patient population. Although disease severity in children infected with Omicron remains to be lower than that in adults, the viral load appears to be equivalent for unvaccinated children and adults.

Concerning the study

The present study included 83 immune-naïve adults and kids. Sixteen of the kid study participants and five inter-related adults from the identical households were infected by Early Clade SARS-CoV-2, whereas 15 immune-naïve children and 11 household adults were infected with the SARS-CoV-2 Delta variant. Moreover, eight immune-naïve children and eight household adults were infected with the Omicron variant.

All study participants who were naturally infected by either Early Clade, Delta, or Omicron strains tested positive by the polymerase chain response (PCR) assay.

Sera were collected from 24 individuals who were vaccinated with ChAdOx1 and BNT162b2. Collection of sera took place inside 35 days following receipt of the second vaccine dose.

All vaccinated adults and kids weren’t previously infected by SARS-CoV-2. Furthermore, 48 healthy and non-inflammatory disorder pre-pandemic control sera samples were included to detect the seropositivity of patients against spike variants.

The detection of spike antibody immunoreactivity within the sera of patients was achieved through the flow cytometry cell-based assay.

Study findings

All PCR-positive patients with no less than 10 days of viral exposure were seropositive for antibodies against the Early Clade Spike (D614) and D614G strains of SARS-CoV-2. The degrees of immunoglobulin A (IgA) and IgG antibodies one to 6 months after viral exposure were similar between children and adults, while higher levels of IgM antibodies were observed in adults.

IgA, IgG, and IgM levels peaked at a median of 30 and 32 days post-viral exposure in adults and kids, respectively. Early Clade Spike IgA and IgG levels endured, even seven months after viral exposure, while spike IgM levels became negative about 163 days after exposure.

Significant differences in spike IgG levels were reported between vaccinated and naturally-infected individuals. Higher levels of Early Clade spike IgG antibodies (D614) were observed in vaccinated children and adults who received the early clade-based BNT162b2 vaccine as in comparison with those that received the ChAdOx1 vaccine.

Reduced levels of spike IgG were observed against VOC spike proteins. Early Clade-infected children exhibited higher titers of the D614G spike IgG, whereas vaccinated children had higher titers against Omicron VOCs. Nonetheless, adults infected with Omicron and Delta possessed high titers across VOCs and were less prone to experience severe COVID-19 as in comparison with children.

Delta-infected children and adults had three- and 1.8-fold higher levels of Early Clade spike IgG, respectively, as in comparison with the Delta spike antigen. Omicron-infected children and adults had five- and three-fold, eight- and four-fold, in addition to 11- and six-fold higher levels of Early Clade spike IgG as in comparison with BA.5, BA.2, and BA.1 spike IgG, respectively.

Antibodies generated through natural infection by the Early Clade SARS-CoV-2 exhibited reduced binding towards all VOCs. Nonetheless, individuals infected with Delta and Omicron exhibited stronger binding towards Gamma, Beta, and Alpha VOCs as in comparison with those infected with Early Clade SARS-CoV-2.

All individuals exhibited limited binding towards Omicron VOCs. Moreover, immunoreactivity among the many vaccinated cohort was just like Early Clade-infected patients.

The presence of the 484Q mutation within the Kappa spike protein, in addition to the 478K mutation within the Delta spike protein, improved antibody binding, which could result in greater immunoreactivity among the many Delta-infected individuals. An analogous result was also observed when lysine (K) at position 484 was replaced with glutamic acid (Q) within the Beta, Eta, and Gamma spike proteins.

Early Clade-infected individuals displayed a powerful binding towards Eta. Strong immunogenicity was also observed for all naturally infected and vaccinated individuals.

Moreover, the presence of N501Y and E484K led to decreased immunogenicity in Omicron, which was further enhanced by the S477N mutation. Nonetheless, this reduction was compensated by Q498R, which is an epistatic contact mutation of N501Y.

Conclusions

Taken together, the study findings reveal vital molecular features concerning broad immunoreactivity and high antibody titers. These observations could be useful in the event of vaccines that may provide broad protective adaptive immune responses, in addition to global serosurveillance efforts.

Limitations

The sample size of naturally infected individuals was small. An extra limitation was that the viral loads were unknown in naturally infected individuals.

Moreover, some participants might need suffered from asymptomatic re-infection through the follow-up, which can have resulted in very low spike antibody titers. Finally, studies on peripheral cells weren’t performed.

*Essential notice

Research Square publishes preliminary scientific reports that will not be peer-reviewed and, subsequently, shouldn’t be considered conclusive, guide clinical practice/health-related behavior, or treated as established information.