The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios
Broadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/12/1/8 |
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| author | Victor Sanchez-Merino Miguel Martin-Serrano Manuela Beltran Beatriz Lazaro-Martin Eloisa Cervantes Manuel Oltra Talia Sainz Felipe Garcia Maria Luisa Navarro Eloisa Yuste |
| author_facet | Victor Sanchez-Merino Miguel Martin-Serrano Manuela Beltran Beatriz Lazaro-Martin Eloisa Cervantes Manuel Oltra Talia Sainz Felipe Garcia Maria Luisa Navarro Eloisa Yuste |
| author_sort | Victor Sanchez-Merino |
| collection | DOAJ |
| description | Broadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic hypermutation in bnAbs and the limited affinity of HIV Env proteins for bnAb germline precursors suggest that extended antigen exposure is necessary for their production. Consequently, HIV vaccine research is exploring complex sequential vaccination strategies to guide the immune response through maturation stages. In this context, the exploration of the factors linked to the generation of these antibodies across diverse age groups becomes critical. In this study, we assessed the anti-HIV-1 neutralization potency and breadth in 108 aviremic adults and 109 aviremic children under 15 years of age who were receiving ART. We used a previously described minipanel of recombinant viruses and investigated the factors associated with neutralization in these individuals. We identified individuals in both groups who were capable of neutralizing viruses from three different subtypes, with greater cross-neutralization observed in the adult group (49.0% vs. 9.2%). In both groups, we observed an inverse association between neutralization breadth and the CD4+/CD8+ ratio, as well as a direct association with the time to ART initiation. However, we found no association with time post-infection, cumulative ART duration, or CD8+ cell levels. The present study demonstrates that children receiving antiretroviral therapy generate broadly neutralizing responses to HIV-1, albeit with lower magnitude compared to adults. We also observed that neutralization breadth is associated with CD4+/CD8+ levels and time to treatment initiation in both children and adults living with HIV-1. Our interpretation of these results is that a delay in ART initiation could have prolonged the antigenic stimulation associated with viral replication and thus facilitate the capacity to elicit long-lasting broadly neutralizing responses. These results corroborate prior findings that show that HIV-1-neutralizing responses can persist for years, even at low antigen levels, implying an HIV-1 vaccine may induce lasting neutralizing antibody response. |
| first_indexed | 2024-03-08T09:45:01Z |
| format | Article |
| id | doaj.art-cfb0d33b75b74570b22c16cf71bbfab7 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-08T09:45:01Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-cfb0d33b75b74570b22c16cf71bbfab72024-01-29T14:25:09ZengMDPI AGVaccines2076-393X2023-12-01121810.3390/vaccines12010008The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ RatiosVictor Sanchez-Merino0Miguel Martin-Serrano1Manuela Beltran2Beatriz Lazaro-Martin3Eloisa Cervantes4Manuel Oltra5Talia Sainz6Felipe Garcia7Maria Luisa Navarro8Eloisa Yuste9National Microbiology Center, Institute of Health Carlos III (ISCIII), 28220 Madrid, SpainNational Microbiology Center, Institute of Health Carlos III (ISCIII), 28220 Madrid, SpainNational Microbiology Center, Institute of Health Carlos III (ISCIII), 28220 Madrid, SpainServicio de Pediatría, Hospital General Universitario Gregorio Marañón, 28009 Madrid, SpainSección de Infectología Pediátrica, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, SpainSección de Patologia Infecciosa Infantil, Hospital Universitari i Politècnic La Fe, 46026 Valencia, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, SpainInfectious Diseases Department, Hospital Clínic, University of Barcelona, 08036 Barcelona, SpainCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, SpainNational Microbiology Center, Institute of Health Carlos III (ISCIII), 28220 Madrid, SpainBroadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic hypermutation in bnAbs and the limited affinity of HIV Env proteins for bnAb germline precursors suggest that extended antigen exposure is necessary for their production. Consequently, HIV vaccine research is exploring complex sequential vaccination strategies to guide the immune response through maturation stages. In this context, the exploration of the factors linked to the generation of these antibodies across diverse age groups becomes critical. In this study, we assessed the anti-HIV-1 neutralization potency and breadth in 108 aviremic adults and 109 aviremic children under 15 years of age who were receiving ART. We used a previously described minipanel of recombinant viruses and investigated the factors associated with neutralization in these individuals. We identified individuals in both groups who were capable of neutralizing viruses from three different subtypes, with greater cross-neutralization observed in the adult group (49.0% vs. 9.2%). In both groups, we observed an inverse association between neutralization breadth and the CD4+/CD8+ ratio, as well as a direct association with the time to ART initiation. However, we found no association with time post-infection, cumulative ART duration, or CD8+ cell levels. The present study demonstrates that children receiving antiretroviral therapy generate broadly neutralizing responses to HIV-1, albeit with lower magnitude compared to adults. We also observed that neutralization breadth is associated with CD4+/CD8+ levels and time to treatment initiation in both children and adults living with HIV-1. Our interpretation of these results is that a delay in ART initiation could have prolonged the antigenic stimulation associated with viral replication and thus facilitate the capacity to elicit long-lasting broadly neutralizing responses. These results corroborate prior findings that show that HIV-1-neutralizing responses can persist for years, even at low antigen levels, implying an HIV-1 vaccine may induce lasting neutralizing antibody response.https://www.mdpi.com/2076-393X/12/1/8HIV-1broadly neutralizing antibodieschildrenARTundetectable viremia |
| spellingShingle | Victor Sanchez-Merino Miguel Martin-Serrano Manuela Beltran Beatriz Lazaro-Martin Eloisa Cervantes Manuel Oltra Talia Sainz Felipe Garcia Maria Luisa Navarro Eloisa Yuste The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios Vaccines HIV-1 broadly neutralizing antibodies children ART undetectable viremia |
| title | The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios |
| title_full | The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios |
| title_fullStr | The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios |
| title_full_unstemmed | The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios |
| title_short | The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios |
| title_sort | association of hiv 1 neutralization in aviremic children and adults with time to art initiation and cd4 cd8 ratios |
| topic | HIV-1 broadly neutralizing antibodies children ART undetectable viremia |
| url | https://www.mdpi.com/2076-393X/12/1/8 |
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