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Vaccination against SARS-CoV-2 should be included in childhood vaccination programs

  • Eskild Petersen
    Correspondence
    Corresponding author at: Institute for Clinical Medicine, Faculty of Health Sciences, University of Aarhus, Palle Juul-Jensens Boulevard 82, DK-8200 Aarhus N., Denmark.
    Affiliations
    Institute for Clinical Medicine, Faculty of Health Science, University of Aarhus, Denmark

    Emerging Infections Task Force, European Society for Clinical Microbiology and Infectious Diseases, Basel, Switzerland

    International Society for Infectious Diseases, Boston, United States
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  • Philippe Buchy
    Affiliations
    GSK Vaccines R&D, 23 Rochester Park, 139234, Singapore
    Search for articles by this author
Open AccessPublished:April 29, 2021DOI:https://doi.org/10.1016/j.ijid.2021.04.082
      Nearly one and a half year into the SARS-CoV-2 pandemic it is clear that the pandemic will not disappear in a few months and indeed annual resurgence has been predicted in a modelling study (
      • Kissler S.M.
      • Tedijanto C.
      • Goldstein E.
      • Grad Y.H.
      • Lipsitch M.
      Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period.
      ).
      Therefore, we must expect that the pandemic will continue in non-immune groups and will possibly continue to evolve to create so called “variants of concern – VOCs” (
      • de Oliveira T.
      • Lutucuta S.
      • Nkengasong J.
      • Morais J.
      • Paixao J.P.
      • Neto Z.
      • et al.
      A novel variant of interest of SARS-CoV-2 with multiple spike mutations detected through travel surveillance in Africa.
      ,
      • Di Caro A.
      • Cunha F.
      • Petrosillo N.
      • Beeching N.J.
      • Ergonul O.
      • Petersen E.
      • Koopmans M.P.G.
      SARS-CoV-2 escape mutants and protective immunity from natural infections or immunizations.
      ,
      • Karim S.S.A.
      • de Oliveira T.
      New SARS-CoV-2 variants — clinical, public health, and vaccine implications.
      ,
      • Tchesnokova V.
      • Kulakesara H.
      • Larson L.
      • Bowers V.
      • Rechkina E.
      • Kisiela D.
      • et al.
      Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants.
      ). Antigenic drift as we know it from influenza is a possibility and require continuous sequencing of a proportion of isolates as the key surveillance tool (
      • Peacock T.P.
      • Penrice-Randal R.
      • Hiscox J.A.
      • Barclay W.S.
      SARS-CoV-2 one year on: evidence for ongoing viral adaptation.
      ). The phenotypic expression should also be monitored as we still ignore how some mutations translate into antigenic changes if we do not use neutralization tests, as we indeed do for influenza.
      Emergence of VOCs is driven by circulation of viruses in non-immunes and the selection pressure from immunity in people with previous infections or vaccination. Therefore, reducing the viral reservoir will be key to reducing the virus’s opportunity to mutate.
      SARS-CoV-2 is a zoonotic virus and hosts also include animals as shown by the large and uncontrollable outbreak in mink farms in Europe and North America (
      • Fenollar F.
      • Mediannikov O.
      • Maurin M.
      • Devaux C.
      • Colson P.
      • Levasseur A.
      • et al.
      Mink, SARS-CoV-2, and the human-animal interface.
      ,
      • Larsen H.D.
      • Fonager J.
      • Lomholt F.K.
      • Dalby T.
      • Benedetti G.
      • Kristensen B.
      • et al.
      Preliminary report of an outbreak of SARS-CoV-2 in mink and mink farmers associated with community spread, Denmark, June to November 2020.
      ). Sporadic infections have been reported in felines and dogs, and although the affinity of SARS-CoV-2 for its receptor varies across species, all mammals express this ACE2 receptor (
      • Wardeh M.
      • Baylis M.
      • Blagrove M.S.C.
      Predicting mammalian hosts in which novel coronaviruses can be generated.
      ,
      • Wei Y.
      • Aris P.
      • Farookhi H.
      • Xia X.
      Predicting mammalian species at risk of being infected by SARS-CoV-2 from an ACE2 perspective.
      ) and new unexpected animal reservoirs may emerge (
      • Prince T.
      • Smith S.L.
      • Radford A.D.
      • Solomon T.
      • Hughes G.L.
      • Patterson E.I.
      SARS-CoV-2 infections in animals: reservoirs for reverse zoonosis and models for study.
      ).
      We know from other viruses that a high degree of immunity in the population is the best guarantee against resurgence, best exemplified by measles that has one of the highest R0 among the current circulating virus and for which the heard immunity is reached when over 95% of the population is vaccinated (
      • Gahr P.
      • DeVries A.S.
      • Wallace G.
      • Miller C.
      • Kenyon C.
      • Sweet K.
      • et al.
      An outbreak of measles in an undervaccinated community.
      ,
      • Majumder M.S.
      • Cohn E.L.
      • Mekaru S.R.
      • Huston J.E.
      • Brownstein J.S.
      Substandard vaccination compliance and the 2015 measles outbreak.
      ). The R0 for SARS-CoV-2 is estimated to be 2.5–3 which mean that circulation would be controlled when 60%–70% of the population is immune (
      • Sridhar D.
      • Gurdasani D.
      Herd immunity by infection is not an option.
      ). In Europe approximately 10% of the population is aged below 20 years and 2.7% below 4 years. In contrast, in Africa these two groups represent approximately 25% and 7% of the population, respectively (
      • PopulationPyramid
      Population pyramids of the world from 1950 to 2100.
      ). Reaching the herd immunity threshold means that if we have to reach immunity in 60–70% of a population to slow down virus circulation, we have to successfully vaccinate 80–100% of all the African adults 20+ years with a vaccine with ∼80% efficacy against any variant. This could be very difficult to achieve for a number of reasons including the logistics and vaccine hesitancy unless we also vaccinate children and adolescents. This group of mostly non-immune individuals (
      • Ladhani S.N.
      • Baawuah F.
      • Beckmann J.
      • Okike I.O.
      • Ahmad S.
      • Garstang J.
      • et al.
      SARS-CoV-2 infection and transmission in primary schools in England in June-December, 2020 (sKIDs): an active, prospective surveillance study.
      ) constitutes at present a potential SARS-CoV-2 reservoir and therefore studies of vaccine safety and efficacy should also focus on younger age groups in order to control the pandemic and limit the emergence of new VOCs (
      • Monod M.
      • Blenkinsop A.
      • Xi X.
      • Hebert D.
      • Bershan S.
      • Tietze S.
      • et al.
      Age groups that sustain resurging COVID-19 epidemics in the United States.
      ).
      Concern has been raised over the efficacy of the different vaccines against the VOCs. Most studies have used in vitro neutralisation assays to demonstrate reduced susceptibility of VOCs to immune sera (
      • Cele S.
      • Gazy I.
      • Jackson L.
      • Hwa S.-H.
      • Tegally H.
      • Lustig G.
      • et al.
      Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma.
      ,
      • Wibmer C.K.
      • Ayres F.
      • Hermanus T.
      • Madzivhandila M.
      • Kgagudi P.
      • Oosthuysen B.
      • et al.
      SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma.
      ;
      • McCallum M.
      • Bassi J.
      • De Marco A.
      • Chen A.
      • Walls A.C.
      • Di Iulio J.
      • et al.
      SARS-CoV-2 immune evasion by variant B.1.427/B.1.429.
      ).
      However, few studies have looked at clinical COVID-19 as the endpoint or added, beside neutralizing antibodies, a measurement of the cellular immune response against these VOCs. Recent studies found that T-cells should recognise newly emerged VOCs and provide some cross-protection (
      • Redd A.D.
      • Nardin A.
      • Kared H.
      • Bloch E.M.
      • Pekosz A.
      • Laeyendecker O.
      • et al.
      CD8+ T cell responses in COVID-19 convalescent individuals target conserved epitopes from multiple prominent SARS-CoV-2 circulating variants.
      ,
      • Woldemeskel B.A.
      • Garliss C.C.
      • Blankson J.N.
      SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63.
      ). A press release from Pfizer/BioNTech indicate that their vaccine is protective against the South African variant, B.1.351 (
      • Pfizer/BionTech
      Pfizer and BioNTech confirm high efficacy and no serious safety concerns through up to six months following second dose in updated topline analysis of landmark COVID-19 vaccine study.
      ;
      • Businesswire
      Pfizer and BioNTech confirm high efficacy and no serious safety concerns through up to six months following second dose in updated topline analysis of landmark COVID-19 vaccine study.
      ). A recent review suggested that “… evidence is growing that these variants share similar combinations of mutations” () meaning that the VOCs are converging i.e. that evolution will result in the same variants in different places.
      The Pfizer/BioNTech coronavirus vaccine is effective in adolescents the companies reported on the 31st March [] and Pfizer, Moderna and Johnson & Johnson have all started trials in children planning immunisations down to the age of 6 months [].
      We believe that it is key to controlling the pandemic including emergence of VOCs that children even down to 2 years of age are immunised.
      For instance, in the United States, 24% of people are under 18 years old [2010 census data]. If most under-18s can not receive the vaccine, 100% of over-18s will have to be vaccinated to reach 76% immunity in the population (
      • Aschwanden C.
      Five reasons why COVID herd immunity is probably impossible.
      ). A recent simulation study from the United States showed that immunising children is important to reduce disease burden overall in the community (
      • Moghadas S.M.
      • Fitzpatrick M.C.
      • Shoukat A.
      • Zhang K.
      • Galvani A.P.
      Simulated identification of silent COVID-19 infections among children and estimated future infection rates with vaccination.
      ).
      This means that if children are indeed a potential source of SARS-CoV-2 infections and vaccination can efficiently prevent transmission, every new birth cohort or approximately 140 million children worldwide needs to be immunised every year (
      • Forbes H.
      • Morton C.E.
      • Bacon S.
      • McDonald H.I.
      • Minassian H.
      • et al.
      Association between living with children and outcomes from covid-19: OpenSAFELY cohort study of 12 million adults in England.
      ,
      • Jones B.E.
      • Brown-Augsburger P.L.
      • Corbett K.S.
      • Westendorf K.
      • Davies J.
      • et al.
      Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection.
      ). Since the direct benefits for the children are limited, this can only be envisaged with vaccines that demonstrate an excellent safety profile in this age group. At present it is not possible to predict if new VOCs will require booster vaccinations with second generation vaccines like we know it from influenza.
      In conclusion: To control the pandemic children should be immunized against SARS-CoV-2 which require that the decision makers start planning how and when to include it in the childhood immunization program in every country.

      Conflict of interests

      Philippe Buchy is an employee of the GSK group of companies and hold shares in the GSK group of companies. This article represents the views of the authors only, and not the views of GSK.

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