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Robert Seder applauds the chronicle of a secret US wartime project to vanquish the disease.

SARS-CoV-2 evolution poses a risk to vaccine and antiviral drug efficacy. Here, Gagne et al. report the development of a variant-agnostic protein, RBD-62, with enhanced ACE2 binding obtained through in vitro evolution and show that RBD-62 inhalation protects nonhuman primates against SARS-CoV-2 Delta challenge.

Seder and colleagues use a self-assembling nanoparticle vaccine and adjuvant to expand stem-like CD8⁺ T cells and trigger potent antitumor responses.

Seder and colleagues show that mucosal adenoviral-vectored vaccine boosting durably prevents infection in nonhuman primates of the highly transmissible, heterologous XBB.1.16 strain of SARS-CoV-2.

Albumin conjugates can enhance drug delivery. Here, the authors repurpose albumin-binding Evans blue to develop nanovaccines that co-deliver adjuvants and tumor neoantigens to antigen-presenting cells in lymph nodes, resulting in potent and durable antitumour immunity in combination immunotherapy.

The beta variant (B.1.351) is to date the most resistant to neutralization of the SARS-CoV-2 variants. Using nonhuman primates, Seder and colleagues demonstrate that double vaccination with a high dose of the lipid nanoparticle vaccine mRNA-1273 protects against infection with the beta variant.

The delivery route and dose of the BCG vaccine profoundly alters the protective outcome after Mycobacterium tuberculosis challenge in non-human primates.

A single dose of the anti-sporozoite monoclonal antibody CIS43LS can achieve durable, sterile protection against Plasmodium falciparum infection.

The authors have previously demonstrated the neutralising capacity of their nanoparticle vaccine, as well as showing protection of non-human primates from SARS-CoV-2 WA-1 infection. In this work, they investigate the ability of their vaccine candidate to neutralise SARS-CoV-2 variants of concern, and protect animals from other sarbecoviruses.

Cancer vaccines that self-assemble into uniform nanoparticles improve tumor clearance.

HIV vaccine development will be facilitated by having animal models that are predictive for translation to humans. Here, the authors use two nonhuman primate models to compare the effects of natural infection and different adjuvants on antigen persistence, diversity and humoral immunity.

The identification of antibodies targeting a conserved site of vulnerability in the Plasmodium falciparum circumsporozoite protein reveals opportunities for passive prevention of malaria in vulnerable individuals and provides insights for rational vaccine design.

Seder and colleagues review the latest scientific advances in understanding how monoclonal antibodies to the circumsporozoite protein prevent malaria and highlight how this emerging intervention can be used alone or alongside existing antimalarial interventions to control malaria across at-risk populations.

Fifty-five percent of individuals vaccinated with an attenuated Plasmodium falciparum sporozoite vaccine remained without parasitemia after controlled human malaria infection one year later; immune correlate analysis in humans and non-human primates suggest a role for liver-resident T cells.

Immunization of macaques with nanoparticle-conjugated receptor-binding domain of SARS-CoV-2 adjuvanted with 3M-052 and alum results in cross-neutralizing antibodies against bat coronaviruses, SARS-CoV and SARS-CoV-2 variants, and may provide a platform for developing pan-coronavirus vaccines.

Vaccine efficacy is enhanced by optimizing the design of polymeric particles for adjuvant and antigen delivery.

Intravenous administration of the BCG vaccine protects non-human primates with pre-existing SIV infection from tuberculosis.

Mucosal vaccines can enhance protection against respiratory viruses. This study describes the immune mechanisms by which intranasal boosting with an unadjuvanted protein increases both B cell immunity and protection in a mouse model of SARS-CoV-2.

The cryo-EM structure of the highly potent malaria antibody L9 reveals a key role of light-chain derived homotypic interactions in antigen binding and parasite inhibition, enabling antibody engineering and next-generation malaria vaccine design.

The PfSPZ Vaccine does not protect infants from infection with Plasmodium falciparum, the major cause of malaria.

The analysis of multiple SIV vaccine regimens in macaques leads to the identification of a key two-amino-acid signature that confers resistance to neutralizing antibodies; a similar mechanism of immune escape is shown to operate in HIV and may explain the limited efficacy seen in HIV vaccine trials.

Neoantigen-specific T cells recognise neoantigen-MHC complexes on target tumour cells. Here, the authors describe a molecular mechanism by which the neoantigen Hsf2 p.K72N is recognised by a corresponding high affinity Hsf2 p.K72N-reactive T cell receptor, 47BE7, from the mouse melanoma line B16F10.

Alter and colleagues show that IgM titers in the plasma and bronchoalveolar lavage fluid represent markers of reduced Mtb burden in rhesus macaques vaccinated intravenously with Bacille Calmette–Guérin.

Immunologist who paved the way to a malaria vaccine.

Innate immune responses to mRNA vaccines are less well understood than adaptive immunity. Here, the authors comprehensively characterize the innate and adaptive immune responses to mRNA-1273 vaccinations in rhesus macaques and show how the vaccine activates interactions among components of the two systems.

A collaborative study demonstrates that, compared with previous SARS-CoV-2 variants, B.1.1.529 isolates cause less infection and disease in mice and hamsters, in agreement with preliminary data from studies in humans.

Malaria remains a disease of global importance, and a fully protective vaccine is elusive. In this Focus Review, Cockburn and Seder describe how insights into the biology of malaria biology may lead to the design of an effective vaccine.

Evolution of the SARS-CoV-2 spike protein receptor-binding domain in vitro recapitulates SARS-CoV-2 variant emergence and produces an effective antiviral spike receptor-binding domain variant.

This Perspective considers present and historical paradigms of therapeutic cancer vaccines and describes a conceptual framework, termed Vax-Innate, to simultaneously generate robust tumour-specific T cell responses and remodel the suppressive tumour microenvironment (TME). The authors detail how this strategy could be achieved through systemic vaccination and by using immune modulators to improve dendritic cell and macrophage function in the TME.

Multiparameter flow cytometry can not only assess the phenotype and magnitude of a T-cell response, but based on effector function, its quality. As discussed here, the quality of a T-cell response is crucial for defining protective cellular immunity, and has great implications for vaccine design.

The SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme provides a real-time risk assessment of SARS-CoV-2 variants with the potential to affect transmission, virulence and resistance to infection- and vaccine-induced immunity.

After primary Leishmania major infection, two populations of CD4⁺ T cells, termed 'effector' and 'central memory' T cells, are generated. Work in mice shows that both populations can mediate protection against subsequent infection, and that persistent infection keeps the effector response robust (pages 1104–1110).

Studies in mice indicate that targeting antigens to dendritic cells (DCs) can elicit strong CD4⁺T cell responses. In this Opinion article, the authors summarize the existing DC-targeting approaches; they discuss whether these vaccines are superior to current vaccines and what future studies should entail to successfully introduce these vaccines into a clinical setting.

Immunization with Plasmodium falciparum sporozoites under chemoprophylaxis can protect against controlled human malaria infection with the same strain for at least 10 weeks, and protection correlates with polyfunctional T-cell memory.