People living with HIV treated during acute infection are the group for whom achieving functional cure appears most viable. Follicular CD8 ⁺ T cells could contribute to HIV reservoir clearance by accessing B cell follicles through CXCR5 expression. This study examines peripheral follicular CD8 ⁺ T cells using flow cytometry, transcriptome analyses, and functional assays in people treated during acute ( n = 37) and chronic ( n = 18) infection, as well as in individuals naturally controlling HIV ( n = 20) and living without HIV ( n = 10). Our results reveal that early, as opposed to late, treatment initiation preserves antiviral effector functions of follicular CD8 ⁺ T cells, which are further enhanced by PD1 inhibition. We also identify a correlation between follicular CD8 ⁺ T cells and intact proviral HIV DNA levels in acute, but not chronic, infection. Longitudinal transcriptomic analysis of peripheral effector cells after 48 weeks of suppressive therapy indicated traits of recent antigen exposure, suggesting potential recirculation into lymphoid tissue. These findings underscore the pivotal role of follicular CD8 ⁺ T cells in anti-HIV responses and support investigating targeted cure strategies, such as anti-PD1 therapy, especially in individuals initiating treatment during acute infection.

Mutations in the spike protein of SARS-CoV-2 can lead to evasion from neutralizing antibodies and affect the efficacy of passive and active immunization strategies. Immunization of mice harboring an entire set of human immunoglobulin variable region gene segments allowed to identify nine neutralizing monoclonal antibodies, which either belong to a cluster of clonally related RBD or NTD binding antibodies. To better understand the genetic barrier to emergence of SARS-CoV-2 variants resistant to these antibodies, escape mutants were selected in cell culture to one antibody from each cluster and a combination of the two antibodies. Three independently derived escape mutants to the RBD antibody harbored mutations in the RBD at the position T478 or S477. These mutations impaired the binding of the RBD antibodies to the spike protein and conferred resistance in a pseudotype neutralization assay. Although the binding of the NTD cluster antibodies were not affected by the RBD mutations, the RBD mutations also reduced the neutralization efficacy of the NTD cluster antibodies. The mutations found in the escape variants to the NTD antibody conferred resistance to the NTD, but not to the RBD cluster antibodies. A variant resistant to both antibodies was more difficult to select and only emerged after longer passages and higher inoculation volumes. VOC carrying the same mutations as the ones identified in the escape variants were also resistant to neutralization. This study further underlines the rapid emergence of escape mutants to neutralizing monoclonal antibodies in cell culture and indicates the need for thorough investigation of escape mutations to select the most potent combination of monoclonal antibodies for clinical use.