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Towards T-cell vaccines for HIV/AIDS Following some high-profile clinical trial failures in recent years, the emphasis in HIV/AIDS vaccine research has shifted away from T-cell-based vaccines that control viral replication towards vaccines that block acquisition of infection. Hansen et al . take a novel route to T-cell-based immunity, using cytomegalovirus (CMV) vectors. They find that vaccination with a rhesus-CMV-based vaccine against simian immunodeficiency virus (SIV) provides long-term protection from SIV challenge in rhesus macaques. Protection seems to be mediated by tissue-resident T-effector memory responses, suggesting that persistent vectors such as CMV may be effective in HIV/AIDS vaccines. The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms 1 , 2 , 3 . However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control 4 . Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors 5 establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T EM ) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV MAC239 infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (≥1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4 + memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8 + T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8 + or CD4 + lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated T EM responses might significantly contribute to an efficacious HIV/AIDS vaccine.

In primates, including humans, mothers engage in face-to-face interactions with their infants, with frequencies varying both within and across species. However, the impact of this variation in face-to-face interactions on infant social development is unclear. Here we report that infant monkeys ( Macaca mulatta ) who engaged in more neonatal face-to-face interactions with mothers have increased social interactions at 2 and 5 months. In a controlled experiment, we show that this effect is not due to physical contact alone: monkeys randomly assigned to receive additional neonatal face-to-face interactions (mutual gaze and intermittent lip-smacking) with human caregivers display increased social interest at 2 months, compared with monkeys who received only additional handling. These studies suggest that face-to-face interactions from birth promote young primate social interest and competency. Like humans, neonatal primates engage in face-to-face interactions with their mothers from an early age. Dettmer and colleagues demonstrate that in monkeys, increasing neonatal face-to-face interactions enhances social interest in infants of two and five months.

Activity in regions of the brain have been correlated with decision making but determining whether such relationships are correlative or causative has been challenging; using a technique to reversibly inactivate brain areas in monkeys reveals that although there is decision-related activity in the lateral intraparietal (LIP) area, LIP is not critical for the perceptual decisions studied here. Limited decision-making potential in brain area LIP Activity in 'area LIP', the lateral intraparietal cortex of the brain, has long been associated with evidence accumulation in sensory decision-making tasks, but a causal role in decision-making has never been established. Leor Katz et al . confirmed that choice-related activity occurs in area LIP and motion-stimulus-related activity in area MT (middle temporal) in rhesus monkeys performing a challenging motion discrimination task. Surprisingly, inactivation in LIP did not impair decision-making, but inactivation of neurons in area MT did. LIP inactivation did influence behaviour in a free-choice task. These findings point to a dissociation between decision-related activity in LIP and the causal role of such activity in decision-making, and indicate that recordings from area LIP in monkeys do not necessarily provide insight into computations involved in decision-making. During decision making, neurons in multiple brain regions exhibit responses that are correlated with decisions 1 , 2 , 3 , 4 , 5 , 6 . However, it remains uncertain whether or not various forms of decision-related activity are causally related to decision making 7 , 8 , 9 . Here we address this question by recording and reversibly inactivating the lateral intraparietal (LIP) and middle temporal (MT) areas of rhesus macaques performing a motion direction discrimination task. Neurons in area LIP exhibited firing rate patterns that directly resembled the evidence accumulation process posited to govern decision making 2 , 10 , with strong correlations between their response fluctuations and the animal’s choices. Neurons in area MT, in contrast, exhibited weak correlations between their response fluctuations and choices, and had firing rate patterns consistent with their sensory role in motion encoding 1 . The behavioural impact of pharmacological inactivation of each area was inversely related to their degree of decision-related activity: while inactivation of neurons in MT profoundly impaired psychophysical performance, inactivation in LIP had no measurable impact on decision-making performance, despite having silenced the very clusters that exhibited strong decision-related activity. Although LIP inactivation did not impair psychophysical behaviour, it did influence spatial selection and oculomotor metrics in a free-choice control task. The absence of an effect on perceptual decision making was stable over trials and sessions and was robust to changes in stimulus type and task geometry, arguing against several forms of compensation. Thus, decision-related signals in LIP do not appear to be critical for computing perceptual decisions, and may instead reflect secondary processes. Our findings highlight a dissociation between decision correlation and causation, showing that strong neuron-decision correlations do not necessarily offer direct access to the neural computations underlying decisions.

To identify molecular mechanisms by which early life social conditions might influence adult risk of disease in rhesus macaques (Macaca mulatta), we analyze changes in basal leukocyte gene expression profiles in 4-mo-old animals reared under adverse social conditions. Compared with the basal condition of maternal rearing (MR), leukocytes from peer-reared (PR) animals and PR animals provided with an inanimate surrogate mother (surrogate/peer reared, SPR) show enhanced expression of genes involved in inflammation, cytokine signaling, and T-lymphocyte activation, and suppression of genes involved in several innate antimicrobial defenses including type I interferon (IFN) antiviral responses. Promoter-based bioinformatic analyses implicate increased activity of CREB and NF-κB transcription factors and decreased activity of IFN response factors (IRFs) in structuring the observed differences in gene expression. Transcript origin analyses identify monocytes and CD4 ⁺ T lymphocytes as primary cellular mediators of transcriptional up-regulation and B lymphocytes as major sources of down-regulated genes. These findings show that adverse social conditions can become embedded within the basal transcriptome of primate immune cells within the first 4 mo of life, and they implicate sympathetic nervous system-linked transcription control pathways as candidate mediators of those effects and potential targets for health-protective intervention.

Recent studies have reported the protective efficacy of both natural 1 and vaccine-induced 2 – 7 immunity against challenge with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in rhesus macaques. However, the importance of humoral and cellular immunity for protection against infection with SARS-CoV-2 remains to be determined. Here we show that the adoptive transfer of purified IgG from convalescent rhesus macaques ( Macaca mulatta ) protects naive recipient macaques against challenge with SARS-CoV-2 in a dose-dependent fashion. Depletion of CD8 + T cells in convalescent macaques partially abrogated the protective efficacy of natural immunity against rechallenge with SARS-CoV-2, which suggests a role for cellular immunity in the context of waning or subprotective antibody titres. These data demonstrate that relatively low antibody titres are sufficient for protection against SARS-CoV-2 in rhesus macaques, and that cellular immune responses may contribute to protection if antibody responses are suboptimal. We also show that higher antibody titres are required for treatment of SARS-CoV-2 infection in macaques. These findings have implications for the development of SARS-CoV-2 vaccines and immune-based therapeutic agents. 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.

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic 1 – 8 . For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques ( Macaca mulatta ) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes 9 , 10 . The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials. 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.

The rhesus macaque is a prime model animal in neuroscience. A comprehensive transcriptomic and open chromatin atlas of the rhesus macaque brain is key to a deeper understanding of the brain. Here we characterize the transcriptome of 416 brain samples from 52 regions of 8 rhesus macaque brains. We identify gene modules associated with specific brain regions like the cerebral cortex, pituitary, and thalamus. In addition, we discover 9703 novel intergenic transcripts, including 1701 coding transcripts and 2845 lncRNAs. Most of the novel transcripts are only expressed in specific brain regions or cortical regions of specific individuals. We further survey the open chromatin regions in the hippocampal CA1 and several cerebral cortical regions of the rhesus macaque brain using ATAC-seq, revealing CA1- and cortex-specific open chromatin regions. Our results add to the growing body of knowledge regarding the baseline transcriptomic and open chromatin profiles in the brain of the rhesus macaque. Non-human primates share many features with humans and are an important animal model in neuroscience. Here, the authors present a comprehensive transcriptomic and open chromatin atlas of the rhesus macaque brain.

Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health. Caloric restriction (CR) delays ageing of model organisms, but whether it works in nonhuman primates has been controversial. Here, the authors pool and reanalyse data from two long-running CR primate studies, concluding that moderate CR indeed improves health and survival of rhesus monkeys.

Our understanding of the neurobiology of primate behaviour largely derives from artificial tasks in highly controlled laboratory settings, overlooking most natural behaviours that primate brains evolved to produce 1 – 3 . How primates navigate the multidimensional social relationships that structure daily life 4 and shape survival and reproductive success 5 remains largely unclear at the single-neuron level. Here we combine ethological analysis, computer vision and wireless recording technologies to identify neural signatures of natural behaviour in unrestrained, socially interacting pairs of rhesus macaques. Single-neuron and population activity in the prefrontal and temporal cortex robustly encoded 24 species-typical behaviours, as well as social context. Male–female partners demonstrated near-perfect reciprocity in grooming, a key behavioural mechanism supporting friendships and alliances 6 , and neural activity maintained a running account of these social investments. Confronted with an aggressive intruder, behavioural and neural population responses reflected empathy and were buffered by the presence of a partner. Our findings reveal a highly distributed neurophysiological ledger of social dynamics, a potential computational foundation supporting communal life in primate societies, including our own. Single-neuron and population activity in the macaque prefrontal and temporal cortex robustly encodes 24 species-typical behaviours, reciprocity in social interactions and social support.

An outbreak of coronavirus disease 2019 (COVID-19) 1 – 3 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 4 , has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus–receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic. Two monoclonal antibodies isolated from a patient with COVID-19 are shown to interfere with SARS-CoV-2–receptor binding, and one displays potent action against this virus in vitro and in a rhesus macaque model.