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Treatment of SHIV-infected monkeys with potent broadly neutralizing anti-HIV-1 monoclonal antibodies resulted in rapid control of viral replication in both peripheral blood and tissues; viral rebound was linked to decreasing antibody concentrations and not the generation of escape mutations, and setpoint viral load following viral rebound remained lower than the initial baseline viral load.

Current vaccines induce broadly cross-reactive cellular immunity against SARS-CoV-2 variants, including Omicron, and provide protection against severe disease despite a substantially reduced neutralizing antibody response.

The phase 2b trial of Merck's recombinant adenovirus type 5–based HIV-1 vaccine was halted as the vaccine seemed to have increased HIV-1 acquisition in vaccine recipients who had preexisting immunity to the adenovirus vector. One theory to explain these results is that the preexisting antibody response to the vector may have been a surrogate for increased vector-specific CD4⁺ T cells, which would have been amplified after vaccination and may have served as increased target cells during subsequent HIV-1 exposure. Daniel Barouch and his colleagues and Michael Betts and his colleagues now challenge this view.

The latent HIV-1 reservoir is the key obstacle for curing HIV-1 infection, but the timepoint at which the HIV-1 reservoir is established is currently unclear. Here, Whitney et al. show in non-human primates that the SIV reservoir in CD4⁺ T cells is seeded within the first 2 days after infection.

The existence of HIV reservoir and ongoing replication despite antiretroviral therapy (ART) represents a barrier for cure efforts. Here, using SIV/SHIV-infected rhesus macaque suppressed with ART for one year, the authors characterize multiple lymphoid and non-lymphoid tissues and show that while the viral reservoir exhibits a wide anatomic heterogeneity, persistent viral transcription is mainly restricted to secondary lymphoid organs.

The origin and nature of rebound HIV-1 virus following antiretroviral therapy (ART) discontinuation still remains unclear. Here, Liu et al. suggest that intact proviral DNA in peripheral blood and lymph node mononuclear cells during ART suppression likely is the source of viral rebound following ART discontinuation.

Recent studies have shown features of antigen-specific memory in mouse NK cells, but it is unclear whether this phenomenon also exists in primates. Barouch and colleagues provide evidence for robust, durable, antigen-specific NK cell memory induced in primates after infection or vaccination.

In this Opinion article, Dan Barouch and Louis Picker discuss recent data regarding the clinical development of novel serotype adenovirus and cytomegalovirus vaccine vectors for use in HIV-1 vaccines.

The authors test several candidate vaccines for Zika virus in mouse models and show that single-shot DNA vaccines and inactivated virus vaccines provide complete protection against Zika virus isolates from Brazil and Puerto Rico.

Reservoirs of virus infection represent the most important reason why HIV-1 cannot be cured with current antiretroviral drugs; now the refractory viral reservoir is shown to be seeded as early as 3 days after infection in a monkey model, even before the virus is detected in the blood.

Protective efficacy of novel vaccine candidates in rhesus monkeys opens new paths for the development of an HIV-1 vaccine.

Intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 in rhesus macaques.

The protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccine expressing the SARS-CoV-2 spike protein in non-human primates is demonstrated.

CV2CoV, a second-generation mRNA COVID-19 vaccine with non-modified nucleosides but optimized non-coding regions, is demonstrated to be effective against SARS-CoV-2 challenge when tested in non-human primates.

Intradermal microneedles for the co-delivery of mRNA and near-infrared fluorescent microparticles are used in combination with deep learning-based image analysis for the simultaneous administration of therapeutics and registry of patient information records into the skin.

The recent epidemic of Zika virus (ZIKV) in the Americas has revealed the devastating consequences of ZIKV infection, particularly in pregnant women. In this Progress article, Barouch and colleagues discuss recent preclinical studies and lessons learned from first-in-human clinical trials with ZIKV vaccines.

In a first-in-human trial of a triple combination of broadly neutralizing antibodies in people living with HIV, 83% of participants maintained virologic suppression for the duration of antibody therapy, with 42% showing virologic suppression for at least 38–44 weeks, despite the decline of serum antibody concentrations to low or undetectable levels.

A single monoclonal antibody is therapeutic and has prophylactic activity against Zika virus in monkeys.

SpaGFT is a spatial omics representation method. It identifies spatially variable genes, enhances gene imputation, detects immunological regions, and characterises variations in secondary lymphoid organs. This method improves predictive power in wide downstream machine-learning tasks.

By integrating the serum concentration of a broadly neutralizing antibody (bNAb) with its in vitro 80% inhibitory concentration, the PT₈₀ biomarker may be used to guide target levels of bNAbs for effective prevention of HIV-1 acquisition.

Vaccine elicted Gag specific cellular immune responses are shown to provide a measure of protection from disease in Mamu-A*01-negative rhesus monkeys challenged with SIV_MAC251.

An analysis identifies human monoclonal antibodies that potently neutralize wild-type SARS-CoV-2 and protect animals from disease, including two that synergize in a cocktail, suggesting that these could be candidates for use as therapeutic agents for the treatment of COVID-19 in humans.

SARS-CoV-2 challenge of rhesus macaques demonstrates that the Ad26.COV2.S vaccine induces robust protection against both the WA1/2020 isolate and the B.1.351 variant of concern.

Replacing parts of a viral capsid protein with those from a related virus can circumvent pre-existing antibody immunity — without compromising its intrinsic imunogenicity.

Adoptive transfer of purified IgG from convalescent macaques protects naive macaques against SARS-CoV-2 infection, and cellular immune responses contribute to protection against rechallenge with SARS-CoV-2.

Analysis of the immunogenicity of the Ad26.COV2.S vaccine against the B1.351 and P.1 SARS-CoV-2 variants of concern shows reduced neutralization antibody titres, but comparable T cell responses and antibody-dependent effector functions.

Automated fabrication of microneedle patch mRNA vaccines for COVID-19 may improve vaccine access.

Vaccine design is challenging when the infectious agent is genetically diverse. Polyvalent 'mosaic' antigens might be used to address this challenge, and these two studies show promising results in monkeys infected with HIV-1 (pages 268–270 and 324–328).

Several COVID-19 vaccines have received emergency approval, but durability of protection is unclear. Here, the authors describe correlates of protection (CoP) for the Ad26.COV2.S vaccine in rhesus macaques and report that CoP predict the protection observed 6 months post vaccination.

The extent of antibody protection against SARS-CoV-2 remains unclear. Here, using a cohort of 120 seroconverted individuals, the authors longitudinally characterize neutralization, Fc-function, and SARS-CoV-2 specific T cell responses, which they show to be prominent only in those subjects that elicited receptor-binding domain (RBD)-specific antibody titers above a certain threshold, suggesting that development of T cell responses to be related to anti-RBD Ab production.

Adenovirus-based vaccination for SARS-CoV-2 has a rare chance to cause thrombosis with thrombocytopenia (TTS). Here the authors compare proteomic and transcriptomic data from vaccinated participants with or without TTS to find distinct activations of coagulation and innate immune pathways in patient with TTS, or following initial or boosting vaccination.

Variant booster vaccines are a strategy to improve protection against SARS-CoV-2. Here, the authors find that both Wuhan-Hu-1-based Ad26.COV2.S or an Omicron-adapted booster vaccine provide robust immune responses and protection against Omicron in NHP.

An antibody-discovery pipeline integrating single-cell mRNA-sequence analysis, bioinformatics, synthetic biology and high-throughput functional analyses enables the rapid discovery of potent human monoclonal antibodies against viral pathogens.

A single dose of a small-molecule HIV capsid inhibitor provides long-term protection from repeated simian–human immunodeficiency virus challenges in macaques and might serve as a novel strategy for HIV prevention in humans.

Antiretroviral therapy alone is insufficient in curing HIV-1 infection, due to latent viral reservoir persistency. Here, authors explore the post-virologic control of combining active and passive immunisation with vesatolimod, in a SHIV-infected rhesus macaque model.

In monkeys infected with an AIDS-like virus, a combination of a broadly neutralizing antibody and an immune stimulator during antiretroviral therapy suppressed viral rebound after antiretroviral drug discontinuation.

Personalized neoantigen vaccination in patients with melanoma elicits durable and specific memory T cell clones that have cytotoxic gene signatures and can diversify to include nonvaccine neoantigen specificities.