Selection of new COVID-19 genotypes following mass vaccination: The Rotavirus model

Lapolla, Pierfrancesco; Familiari, Pietro; Bruzzaniti, Placido
doi:10.1016/j.vacun.2021.10.004
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0005" class="elsevierStylePara elsevierViewall">RNA-based vaccines have been shown to be safe and effective in protecting humans from severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41; infection&#46; Other vaccines have already been shown to be effective in preventing infection&#46;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> Concerns arose over four variants and other nine are currently being studied&#46; The Delta variant&#44; characterized by peculiar mutations of the Spike protein&#44; was found in nearly 95&#37; of sequenced cases and in 92&#37; of genotyped cases analyzed between 7 and June 21&#44; 2021&#46;<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a> However&#44; the two Covid-19 vaccines which are the BNT162b2 and ChAdOx1 nCoV-19&#44; resulted in being highly effective against the Delta variant after the double shot vaccine injection&#44;<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> therefore&#44; the current mass vaccination campaign aims at immunizing the population with a two doses vaccine injection&#46; Regarding the viral mutation and replication principles&#44; even if the mutation frequency is independent of the population &#40;intrinsic property&#41;&#44; the probability to find an individual mutation or indel is directly proportional to the spread of the circulating virus &#40;extrinsic property&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a> In case of generation of a new resistant variant&#44; large-scale vaccination would then exert a selective action which would favor its prevalence over the dominant strains in a short time&#46; If a vaccine-resistant variant develops at the time between vaccination and exposure&#44; the vaccinated individual could be left unprotected&#46; In the case of widespread of a resistant viral variant&#44; the vaccination campaign might be retroactively ineffective&#46; Moreover&#44; since most of COVID-19 vaccine target either the viral Spike protein or the Spike protein receptor binding domain&#44; the development of a resistance could destabilize at the same time the effectiveness of other vaccines&#46; This phenomenon in the case of antimicrobial drugs is referred to as &#8220;cross&#8221; or &#8220;collateral&#8221; resistance&#46;<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> Large-scale vaccination can unbalance the relationships between the host and the virus by selecting different genotypes&#44; drastically reducing the spread of dominant strains&#46;<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a> Rotavirus vaccination campaigns can be considered as an important epidemiological model for evaluating how genotype fluctuations of SARS-CoV-2 can occur in the post-vaccine era&#46; In the vaccination campaigns against Rotaviruses carried out in Finland&#44; a strong impact was observed on the reduction of the disease burden measured as hospitalization and outpatient episodes among the very young&#46; However&#44; this led to the selection of non-dominant genotypes with a shift in the incidence in the age groups&#46;<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a> New genotypes seem to have appeared to replace the dominant genotypes in the pre-vaccination era&#46; It is interesting to evaluate the prevalence of the G1 and non-G1 genotypes in consecutive rotavirus seasons&#44; as RotarixTM mainly has been used in Belgium&#46; A significant increase in the prevalence of the G2 genotype has been observed &#40;above 30&#37;&#41; since the introduction of the rotavirus vaccines&#46; This remained the case for the 2007&#47;2008 and 2008&#47;2009 seasons&#46; Very low numbers of G2 strains were found in seasons before vaccine introduction &#40;1999&#47;2006&#41; and the prevalence of G2 genotypes never surpassed 20&#37; in contrast to other circulating genotypes&#46;<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> Similar observations have been reported in the USA<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a> and in China where a continuous evolution of rotavirus has been highlighted&#46;<a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a> Regarding the hepatitis A immunization&#44; vaccination programs have been run among preadolescents in the Catalonia Autonomous Community of Spain&#46; Four variants were isolated which were localized very close to the immune-dominant site and to residues substituted in two MAR mutants &#40;C6 and P29 monoclonal antibody-resistant&#41;&#46; This shows a viral phenotype resistant to commercial vaccines protection&#46;<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a> It is interesting to note that several studies have been looking at important animal pathogens&#44; such as bovine respiratory Syncytial virus &#40;BRSV&#41;&#44; bovine herpesvirus-1 &#40;BoHV-1&#41;&#44; foot and mouth disease virus &#40;FMDV&#41;&#44; and Marek&#39;s disease virus &#40;MDV&#41;&#46; These studies reported evidence regarding the development of viral pathogens within vaccinated population&#44; and found evidence that the evolution of a pathogen widespread in a population is not only an important implication for vaccine resistance but also it might contribute to the generation of new variants with different pathogenicity or altered host tropism&#46;<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> A clear example of viral mutation is represented by the case of BRSV&#46; This virus combines a high rate of sequence evolution that provides local genetic differentiation and justifies the related geographic groupings seen in phylogenetic trees&#44; with an elevated high rate of amino acid changes in some other regions of the G protein&#46; Considering that G protein are antigenic&#44; these modifications allow the virus to possibly escape previously established immunity&#44; controlled in vitro with HRSV&#44; and isolates from countries where vaccination campaign is extensively applied demonstrate large changes in the amino acid sequences found in these specific regions&#46;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> A further study supports evolutionary evidence in favor of the Classical swine fever virus &#40;CSFV&#41; vaccination strategies based on genotype 1 strains which results in advantageous immune environments for the survival of genotype 2 CSFV strain&#44; constantly evolving in order to escape the immune system&#46; Nevertheless&#44; other experimental challenge studies revealed that current vaccine strains which are based on genotype 1 isolates&#44; could result in protecting against the current CSFV strains&#46; Therefore&#44; in this example&#44; effective and efficient vaccination strategies are necessary to diminish and control the development of CSFV in swine herds and to prevent the generation of vaccine-escaping variants&#46;<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a> Another example of the molecular variation related to vaccination is represented by the vaccines against porcine circovirus 2 &#40;PCV2&#41; where the PCV2 populations variability showed to be different in samples obtained from vaccinating and non-vaccinating farms&#46;<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> The high mortality rate due to the infection and socio-economic impact related to the SARS-CoV-2 pandemic leads to massive vaccination campaigns that will eventually affect the dominant viral cluster&#46; This process can facilitate the selection of non-dominant genotypes resistant to immunization&#46; The spread of non-dominant viral genotypes may change the clinical and epidemiological aspects of the infection&#46;<a class="elsevierStyleCrossRef" href="#bib82"><span class="elsevierStyleSup">18</span></a> Currently&#44; there is no evidence supporting that the vaccination of the entire population can be effective&#46; More generally&#44; a universal vaccine has never been obtained for influenza infection&#46;<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> Mainly all vaccination campaigns were carried out on risk groups&#59; the SARS-CoV-2 vaccination campaign is the first one extended to the entire population&#46; The aim of the vaccination campaign should not be only to prevent the infection of one of the COVID-19 genotypes but to prevent deaths related to it&#46;<a class="elsevierStyleCrossRef" href="#bib81"><span class="elsevierStyleSup">17</span></a> The results of Rotavirus vaccination campaigns can be used to predict the effects of SARS-CoV-2 vaccination campaigns&#46; The reported immunization campaigns&#44; that may be used as models for the SARS-CoV-2 vaccination programmes&#44; have showed that immunization can have a selective action on resistant viral genotypes&#44; promoting their prevalence compared to dominant genotypes&#46; Therefore&#44; continuous surveillance is necessary to identify the prevalence of new genotypes resistant to the immunization process&#46;<a class="elsevierStyleCrossRef" href="#bib83"><span class="elsevierStyleSup">19</span></a></p><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0005">Funding</span><p id="p0010" class="elsevierStylePara elsevierViewall">Pierfrancesco Lapolla is supported by The Foundation Blanceflor Boncompagni Ludovisi&#44; n&#233;e Bildt scholarship&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Contributorship</span><p id="p0015" class="elsevierStylePara elsevierViewall">PL and PB for article design&#44; literature search&#44; writing and responsibility for overall content&#46; PF for manuscript revision&#46;</p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Declaration of interests</span><p id="p0020" class="elsevierStylePara elsevierViewall">The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper&#46;</p></span></span>"
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