Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins—when expressed by simian-human immunodeficiency viruses in rhesus macaques—elicited patterns of Env-antibody coevolution strikingly similar to those in humans. This included conserved immunogenetic, structural and chemical solutions to epitope recognition and precise Env-am ino acid substitutions, insertions and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2-apex mode of recognition like that of human bNAbs PGT145/PCT64-35S. Another rhesus antibody bound the CD4-binding site by CD4 mimicry mirroring human bNAbs 8ANC131/CH235/VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.
C oronavirus disease (COVID-19) is typically diagnosed by reverse transcription PCR (RT-PCR) amplifi cation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA from nasopharyngeal fl uids (1). RT-PCR yields cycle threshold (C t ) values that are inversely correlated with viral loads (2) and thus provide an estimate of the number of SARS-CoV-2 RNA copies in the sample. Serologic assays complement COVID-19 diagnosis by documenting past infections. In most persons, binding and neutralizing antibodies develop within 1-3 weeks after onset of symptoms (3), and titers correlate with disease severity (4).Initial serosurveys identifi ed antibodies in nearly 100% of persons with RT-PCR-confi rmed SARS-CoV-2 infection (5). However, more recent studies have shown that seroconversion rates are surprisingly variable (6-10). For example, a multicenter study from Israel reported that 5% of participants remained seronegative despite a positive test result on a nasal swab specimen (6). In contrast, a seroprevalence study from New York found that 20% of persons with a positive RT-PCR test result did not seroconvert (8). Another study from Germany reported that 85% of confi rmed infected COVID-19 contacts failed to develop antibodies (9). To examine the reasons for these differences, we investigated the relationship between seroconversion and demographic, clinical, and laboratory data in a convenience sample of convalescent persons recruited at the University of Alabama at Birmingham (Birmingham, Alabama, USA) in 2020.
The StudyWe studied 72 persons, all of whom had a previous positive RT-PCR test but were symptom-free for >3 weeks before blood was collected for testing (Table ). Only 2 persons (3%) reported no symptoms, whereas 13 (18%) persons reported mild disease, 48 (67%) reported moderate disease, and 9 (12%) reported severe disease (Appendix Table 1, https://wwwnc.cdc.gov/ EID/article/27/9/21-1024-App1.pdf).We tested plasma samples (n = 144) collected at enrollment and follow-up visits for antibodies to the spike protein by using a validated ELISA (Appendix). Only 46 of the 72 participants had detectable IgG responses, IgA responses, or both (Table ); reciprocal endpoint titers ranged from 182 to >312,500 (Appendix Table 2). Analysis of the same samples for receptor-binding domain (RBD) and nucleocapsid (N)
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