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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In 1960&#44; Francis<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#44; studying the response to flu revaccination&#44; observed that those who were revaccinated presented with a lesser immune response than those who had not previously been vaccinated&#46; He proposed the term &#8220;original antigenic sin&#8221; &#40;OAS&#41; for this phenomenon in which&#44; after a second exposure to a different antigen variant of the same virus&#44; the immune system responded with antibodies of a lesser intensity and specificity&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">This phenomenon&#44; also called &#8220;Hoskins&#8217; paradox&#8221; or &#8220;negative interference&#44;&#8221; means that with another vaccination for a virus that uses strains which are antigenically different&#44; the immune system basically responds with the already-present antibodies &#40;immunological laziness&#41; and&#44; to a lesser extent&#44; with new antibodies induced by the new vaccine&#44; decreasing the protective efficacy of the second vaccine<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a>&#46; In this manner&#44; the immunological footprint left by the first contact with the virus will determine future responses to it&#44; given that it will be fixed by the first immune response<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">OAS increases through vaccination with low doses of an antigen&#44; as memory B cells sequester the immunogens which activate new B cells&#44; despite the fact that the latter have a high affinity and capacity for antibody production when faced with the new antigen<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; Thus&#44; OAS could determine the immune evasion of new antigenic variants in people who have already had the infection or have previously been vaccinated against another variant&#46; This negative effect has already been observed in other viral infections apart from the flu&#44; such as dengue virus and human papillomavirus<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">We must study the possible effect of OAS in depth during the process of revaccination against new variants of SARS-CoV-2<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; It has be proposed that antigenic distance could explain the way in which efficacy of vaccines may be related to prior vaccination&#46; Indeed&#44; vaccines with distant antigenic variants may not be controlled by the prior immune response&#44; which would have created immune &#8220;imprinting&#8221; that would determine the initial formation of antibodies against the first recognized variant<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In revaccination&#44; the immune system uses the initial imprinting and simply modifies the B cell clonotypes&#44; adapting them to the new antigen&#46; This phenomenon would leave individuals with a limited&#44; pre-established immune response such that revaccination would produce an immune response that is always lesser than what is induced by first contact with the virus<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46; This phenomenon would not be a problem if the immunological memory produced neutralizing antibodies against new vaccine antigens&#46; However&#44; it would be a problem if they were non-neutralizing antibodies&#44; such as those induced by human coronaviruses other than SARS CoV-2<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Lessler et al&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> have proposed an alternative hypothesis to OAS that they call &#8220;antigenic seniority&#8221; to explain the lesser immune response following revaccination&#46; This hypothesis establishes the existence of a dominant antibody response as a consequence of repeated exposures to the same antigens more so than the existence of an immune imprinting against the first viral antigen&#46; However&#44; it does not seem that in the case of human coronaviruses&#44; repeated exposure determines this type of response<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;9</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Due to the constant genetic evolution of SARS-CoV-2&#8212;both natural and due to pressure from the human immune system&#8212;it is possible that in the near future&#44; we may have to revaccinate the population against variants that become predominant<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; In this context&#44; it is to be expected that OAS would hinder achieving adequate protection&#44; favoring the spread of the virus despite mass vaccination&#46; Thus&#44; the selection of a similar antigenic variant already recognized by a large part of the population for a new vaccine could lead to the following consequences&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a&#41;</span><p id="par0040" class="elsevierStylePara elsevierViewall">The induction of back-boosting&#44; that is obtaining increased protective immunity in response to a second stimulation of the memory B cells as a consequence of the presence of common antigens or antigens shared between them&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b&#41;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Obtaining a non-protective immune response due to the induction of non-neutralizing antibodies in response to the new antigenic variant&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c&#41;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Use of a multiantigenic vaccine that could mask the protective immune response &#40;antigen masking&#41; against some viral components if any of them had previously been detected by the immune system<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p></li></ul></p><p id="par0055" class="elsevierStylePara elsevierViewall">To evaluate the efficacy of revaccination and the possible impact of OAS on SARS-CoV-2&#44; a clinical trial has been started in individuals vaccinated with the mRNA-1273 vaccine&#46; Two possibilities are going to be studied&#58; in one&#44; individuals will only receive one dose of the new vaccine adapted to the South African variant &#40;mRNA-1273&#46;351&#41; and in the other&#44; one dose of the combination of mRNA-1273&#160;&#43;&#160;mRNA-1273&#46;351<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46; The results will provide information on the role of prior antigen imprinting on the quantity and quality of the immune response to the new genetic variant of SARS-CoV-2&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">At this time&#44; it is very difficult to forecast the possible impact of OAS on future revaccinations against SARS-CoV-2&#44; but we must begin to analyze it and find a way to improve the antigen presentation of the new variants of this virus&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0065" class="elsevierStylePara elsevierViewall">No funding has been received for the creation of this article&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The author declares that there are no conflicts of interest&#46;</p></span></span>"
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Editorial
Possible effect of the “original antigenic sin” in vaccination against new variants of SARS-CoV-2
Posible efecto del «pecado antigénico original» en la vacunación frente a las nuevas variantes del SARS-CoV-2
J. Reina
Unidad de Virología, Servicio de Microbiología, Hospital Universitario Son Espases, Facultad de Medicina (UIB), Palma de Mallorca, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In 1960&#44; Francis<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#44; studying the response to flu revaccination&#44; observed that those who were revaccinated presented with a lesser immune response than those who had not previously been vaccinated&#46; He proposed the term &#8220;original antigenic sin&#8221; &#40;OAS&#41; for this phenomenon in which&#44; after a second exposure to a different antigen variant of the same virus&#44; the immune system responded with antibodies of a lesser intensity and specificity&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">This phenomenon&#44; also called &#8220;Hoskins&#8217; paradox&#8221; or &#8220;negative interference&#44;&#8221; means that with another vaccination for a virus that uses strains which are antigenically different&#44; the immune system basically responds with the already-present antibodies &#40;immunological laziness&#41; and&#44; to a lesser extent&#44; with new antibodies induced by the new vaccine&#44; decreasing the protective efficacy of the second vaccine<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a>&#46; In this manner&#44; the immunological footprint left by the first contact with the virus will determine future responses to it&#44; given that it will be fixed by the first immune response<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">OAS increases through vaccination with low doses of an antigen&#44; as memory B cells sequester the immunogens which activate new B cells&#44; despite the fact that the latter have a high affinity and capacity for antibody production when faced with the new antigen<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; Thus&#44; OAS could determine the immune evasion of new antigenic variants in people who have already had the infection or have previously been vaccinated against another variant&#46; This negative effect has already been observed in other viral infections apart from the flu&#44; such as dengue virus and human papillomavirus<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">We must study the possible effect of OAS in depth during the process of revaccination against new variants of SARS-CoV-2<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; It has be proposed that antigenic distance could explain the way in which efficacy of vaccines may be related to prior vaccination&#46; Indeed&#44; vaccines with distant antigenic variants may not be controlled by the prior immune response&#44; which would have created immune &#8220;imprinting&#8221; that would determine the initial formation of antibodies against the first recognized variant<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In revaccination&#44; the immune system uses the initial imprinting and simply modifies the B cell clonotypes&#44; adapting them to the new antigen&#46; This phenomenon would leave individuals with a limited&#44; pre-established immune response such that revaccination would produce an immune response that is always lesser than what is induced by first contact with the virus<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#46; This phenomenon would not be a problem if the immunological memory produced neutralizing antibodies against new vaccine antigens&#46; However&#44; it would be a problem if they were non-neutralizing antibodies&#44; such as those induced by human coronaviruses other than SARS CoV-2<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Lessler et al&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> have proposed an alternative hypothesis to OAS that they call &#8220;antigenic seniority&#8221; to explain the lesser immune response following revaccination&#46; This hypothesis establishes the existence of a dominant antibody response as a consequence of repeated exposures to the same antigens more so than the existence of an immune imprinting against the first viral antigen&#46; However&#44; it does not seem that in the case of human coronaviruses&#44; repeated exposure determines this type of response<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;9</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Due to the constant genetic evolution of SARS-CoV-2&#8212;both natural and due to pressure from the human immune system&#8212;it is possible that in the near future&#44; we may have to revaccinate the population against variants that become predominant<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; In this context&#44; it is to be expected that OAS would hinder achieving adequate protection&#44; favoring the spread of the virus despite mass vaccination&#46; Thus&#44; the selection of a similar antigenic variant already recognized by a large part of the population for a new vaccine could lead to the following consequences&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a&#41;</span><p id="par0040" class="elsevierStylePara elsevierViewall">The induction of back-boosting&#44; that is obtaining increased protective immunity in response to a second stimulation of the memory B cells as a consequence of the presence of common antigens or antigens shared between them&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b&#41;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Obtaining a non-protective immune response due to the induction of non-neutralizing antibodies in response to the new antigenic variant&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c&#41;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Use of a multiantigenic vaccine that could mask the protective immune response &#40;antigen masking&#41; against some viral components if any of them had previously been detected by the immune system<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46;</p></li></ul></p><p id="par0055" class="elsevierStylePara elsevierViewall">To evaluate the efficacy of revaccination and the possible impact of OAS on SARS-CoV-2&#44; a clinical trial has been started in individuals vaccinated with the mRNA-1273 vaccine&#46; Two possibilities are going to be studied&#58; in one&#44; individuals will only receive one dose of the new vaccine adapted to the South African variant &#40;mRNA-1273&#46;351&#41; and in the other&#44; one dose of the combination of mRNA-1273&#160;&#43;&#160;mRNA-1273&#46;351<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46; The results will provide information on the role of prior antigen imprinting on the quantity and quality of the immune response to the new genetic variant of SARS-CoV-2&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">At this time&#44; it is very difficult to forecast the possible impact of OAS on future revaccinations against SARS-CoV-2&#44; but we must begin to analyze it and find a way to improve the antigen presentation of the new variants of this virus&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0065" class="elsevierStylePara elsevierViewall">No funding has been received for the creation of this article&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The author declares that there are no conflicts of interest&#46;</p></span></span>"
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