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A new study reports that specific combinations of killer immunoglobulin-like receptor and HLA-B alleles influence AIDS progression and plasma HIV RNA levels in HIV-infected individuals. These results suggest that natural killer cells have an important role in recognizing and limiting HIV infection.

After early initiation of anti-retroviral therapy in infants infected with HIV-1 in utero, some children sustain undetectable virus levels, despite treatment interruption, which associated with distinct features of the transmitted virus.

Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.

Questions have arisen as to whether patients with severe COVID-19 disease can generate a T cell response against SARS-CoV-2. Tao Dong and colleagues report that convalescent patients with COVID-19 harbor functional memory CD4⁺ and CD8⁺ T cells that recognize multiple epitopes that span the viral proteome. CD4⁺ T cells predominated the memory response in patients with severe disease, whereas higher proportions of CD8⁺ T cells were found in patients with mild disease.

Sex differences in the immune response to vaccines and infections have been well described in children and adults. Here the authors describe, in a cohort of 177 HIV-infected infants, innate immune sex differences in fetal life that increase female susceptibility to intrauterine HIV infection and increase the chances of subsequent HIV remission in infected males.

Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.

The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.

HIV infection can be partially regulated by the host immune system; however whether B cells contribute to this response is unclear. Huanget al. show that transient depletion of B cells can result in an increase in HIV viral load suggesting that these immune cells do participate in the control of HIV infection.

Infections with HIV, hepatitis B virus and cytomegalovirus have markedly different outcomes depending on whether they are acquired during infancy or adult life. Information about the differences between antiviral immune responses in early and later life that can be gained from these examples should inform the development of new therapeutic strategies.

The outcome of HIV infection is strongly influenced by the particular HLA genes expressed by the infected individual. Here, the authors draw on this association to evaluate what might constitute an effective CD8⁺T-cell response and how it might guide vaccine design.

Anecdotal reports of HIV-infected children who have continued to control viral replication after discontinuing antiretroviral therapy have led to the hope that unique factors associated with paediatric infection might offer greater potential for HIV cure in children than in adults.

Various host factors may impact within-host pathogen evolution. Here, the authors develop a Bayesian approach for identifying host-pathogen interactions using large data sets of pathogen diversity, and apply it to investigate HLA-induced selection in the HIV-1 genome.

This paper traces the adaptation of HIV to HLA alleles in 2,500 HIV-infected subjects and demonstrates a strong correlation between the prevalence of escape mutations within well characterized epitopes and the prevalence of the respective HLA alleles, thereby providing evidence that the virus is indeed adapting to effective immune responses.

Jonathan Carlson and colleagues report that pre-adaptation of HIV to a recipient's major histocompatibility complex class I alleles impairs immune control of the virus.

Cross-neutralization assays of early variants and the 501Y.V2 variant of SARS-CoV-2 show that plasma from individuals infected with 501Y.V2 effectively neutralizes all variants, indicating that a vaccine that targets 501Y.V2 may also be effective against other SARS-CoV-2 variants.

Why is the immune system ultimately unable to control HIV infection? Many of the immune system's cytotoxic T lymphocytes detect an HIV-infected cell by its expression of a peptide from the HIV protein Tat. In so doing, the lymphocytes may encourage the evolution of Tat, allowing HIV to escape immune detection.