Abstract
BackgroundA notable feature of coronavirus disease 2019 (COVID-19) is that children are less susceptible to severe disease. Children are known to experience more infections with endemic human coronaviruses (HCoVs) compared to adults. Little is known whether HCoV infections lead to cross-reactive anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies.MethodsWe investigated the presence of cross-reactive anti–SARS-CoV-2 IgG antibodies to spike 1 (S1), S1-receptor-binding domain (S1-RBD), and nucleocapsid protein (NP) by enzyme-linked immunosorbent assays, and neutralizing activity by a SARS-CoV-2 pseudotyped virus neutralization assay, in prepandemic sera collected from children (n = 50) and adults (n = 45), and compared with serum samples from convalescent COVID-19 patients (n = 16).ResultsA significant proportion of children (up to 40%) had detectable cross-reactive antibodies to SARS-CoV-2 S1, S1-RBD, and NP antigens, and the anti-S1 and anti–S1-RBD antibody levels correlated with anti–HCoV-HKU1 and anti–HCoV-OC43 S1 antibody titers in prepandemic samples (P < .001). There were marked increases of anti–HCoV-HKU1 and - OC43 S1 (but not anti-NL63 and -229E S1-RBD) antibody titers in serum samples from convalescent COVID-19 patients (P < .001), indicating an activation of cross-reactive immunological memory to β-coronavirus spike.ConclusionsWe demonstrated cross-reactive anti–SARS-CoV-2 antibodies in prepandemic serum samples from children and young adults. Promoting this cross-reactive immunity and memory response derived from common HCoV may be an effective strategy against SARS-COV-2 and future novel coronaviruses.
Highlights
The b-herpesvirus, human cytomegalovirus (HCMV), infects most individuals during their lifetime, yet results in disease only in those whose immune system is immature, impaired by immunosuppressive drugs or the human immunodeficiency virus (HIV)
We have evaluated the adjuvant effects of aluminum phosphate and coadministered CpG ODN on the generation of gpUL55-specific and neutralizing antibody responses after inoculation of mice with an HCMV gpUL55 DNA vaccine
We have developed a prototype HCMV DNA vaccine, pRc/CMV2-gB, and evaluated its immunogenicity in a BALB/c mouse system
Summary
The b-herpesvirus, human cytomegalovirus (HCMV), infects most individuals during their lifetime, yet results in disease only in those whose immune system is immature, impaired by immunosuppressive drugs or the human immunodeficiency virus (HIV). A recent report from the Institute of Medicine, Washington, D.C., strongly supports the development of a HCMV vaccine based on the economic impact of the disease caused by this virus [Stratton et al, 2001]. In a study reported recently by our group, using a mathematical modeling approach, we calculated that the critical vaccination proportion required for eradication of HCMV in the developed world lies between 59% and 62%. This finding demonstrates that HCMV could be eradicated from the population, given the current routine pediatric immunization rates ($90%) by a vaccine with only 65–68% efficacy at preventing primary infection [Griffiths et al, 2001]
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