Clinical trials

Clinical trial statistics underlie the central decision-making process for whether a therapeutic approach can enter the clinic, but the nuances of this field may not be widely understood. Furthermore, how the statistics used in clinical trials differ from preclinical approaches and why they differ is not always clear. Here, three experts discuss the intricacies of clinical trial statistical planning and analysis as well as common issues that arise and emerging trends. The experts are Dr Tao Chen (Senior lecturer in Biostatistics at the Liverpool School of Tropical medicine), Professor Li Chao (Professor in Biostatistics at Xi’an Jiaotong University) and Professor Yang Wang (Professor in Biostatistics at the Chinese Academy of Medical Sciences and Peking Union Medical College). They have a diverse range of backgrounds across biostatistics and have been involved in numerous clinical trials of varying types.

Many aspects of human health and disease are influenced by sex as a biological variable and gender as a social construct. A recent study from Nature Communications reported the landscape of outcome comparisions by sex in oncology clinical trials, highlighting the need for a more thorough reporting of sex differences.

Professor Sabine Oertelt-Prigione has been working in the field of sex and gender-sensitive research for the last 15 years. Her current work is focused on trying to understand how sex and gender-sensitive medicine can be successfully implemented in research and practice as well as methods to investigate gender in medical research. Dr. Brandon Turner is a resident physician in the Department of Radiation Oncology at Massachusetts General Hospital and Brigham and Women’s Hospital. He has conducted and is involved in numerous studies looking to evaluate race and ethnicity reporting and representation in clinical trials. In this interview for Nature Communications, Sabine Oertelt-Prigione, and Brandon Turner share their knowledge about the biases that can occur in clinical trials and how they can be minimized.

Since its inception 10 years ago Nature Communications has strived to publish papers of high quality and relevance to communities of researchers across the whole of the natural sciences. In more recent years, we have happily seen an increase in the submission and publication of clinical research studies. To serve the clinical community to the best of our ability we have clarified our guide to authors on what we expect to see on submission of clinical research papers and we are launching a Clinical Collection that presents under one umbrella a selection of the interesting papers we have published in this area

Ruth Plummer is Professor of Experimental Cancer Medicine, Newcastle University, and an honorary consultant medical oncologist in Newcastle Hospitals NHS Foundation Trust. She directs the Sir Bobby Robson Cancer Trials Research Centre and leads the Newcastle Experimental Cancer Medicine Centre and CRUK Newcastle Cancer Centre. She has taken multiple agents targeting DDR into the clinic, including the first-in-human PARP and ATR inhibitors. In addition, she has an active clinical practice treating skin cancer, both in the advanced and adjuvant settings and with an associated clinical trials portfolio including both early and later phase trials. In this interview for Nature Communications, Ruth Plummer shares her knowledge about the basic principles for the design of clinical trials and how they should be reported.

Immune checkpoint blockade (ICB) has shown promising activity in patients with advanced endometrial cancer, however its potential in the context of loco-regional disease remains unclear. Here the authors report the results of a phase I trial of neoadjuvant pembrolizumab (anti-PD1) in patients with mismatch repair deficient resectable endometrial cancer.

TGFβ can promote the development of drug resistance and growth of multiple myeloma (MM). Here the authors report the results of a phase 1b trial of the TGFβ type I receptor kinase inhibitor vactosertib in combination with pomalidomide in patients with relapsed and/or refractory (MM) who had received >2 lines of chemoimmunotherapy.

Most patients with metastatic melanoma still develop primary or acquired resistance to immune checkpoint inhibition (ICI). Here the authors report the results of a phase II trial of cryoablation and ICI in patients with unresectable melanoma progressing on ICI.

Monotherapy with immune checkpoint inhibitors has shown limited clinical activity in patients with microsatellite stable (MSS) colorectal cancer (CRC). Here the authors report the results of a clinical trial of tislelizumab (anti-PD1) in combination with cetuximab (anti-EGFR) and irinotecan in patients with refractory MSS and RAS wild-type metastatic CRC.

Combinations of radiotherapy and immune checkpoint inhibitors have been explored for the treatment of patients with non-small cell lung cancer (NSCLC). Here the authors report the results of a phase 2 trial of sintilimab (anti-PD1) in combination with stereotactic body radiotherapy and GM-CSF in metastatic NSCLC.

Although immune checkpoint blockade is a standard treatment for patients with malignant mesothelioma, only a minority of patients exhibit radiological response. In a phase II clinical trial (MIST4) investigating the efficacy, safety and molecular correlates of response following treatment with atezolizumab and bevacizumab, the authors demonstrate that the gut microbiota may modulate responsiveness to treatment.

Chemo-immunotherapy regimens are now recommended as first-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC), however survival outcomes remain unsatisfactory. Here the authors report the results of a phase 2 trial of toripalimab (anti-PD1) plus chemotherapy and radiotherapy in patients with treatment-naïve advanced ESCC.

Lymphoplasmacytic lymphoma is a B-cell low-grade lymphoma with no approved standard therapy. Here the authors report a non-randomized phase 1 clinical trial performing early intervention with personalized neoantigen vaccines in asymptomatic patients and associating clinical efficacy with successful perturbation of the tumor immune microenvironment.

Preclinical studies indicate that simultaneous HER2 and VEGF blockade may be beneficial in gastroesophageal adenocarcinoma (GEA). Here, the authors report the efficacy and biomarker analysis of a phase II clinical trial investigating the combination of bevacizumab (anti-VEGF) and standard-of-care CAPOX (capecitabine, oxaliplatin) and trastuzumab in previously untreated advanced HER2 + GEA.

A combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is a commonly used regimen for patients with Richter transformation (RT), an aggressive lymphoma with a poor prognosis. Here the authors report the results of a phase 2 clinical trial of blinatumomab (an anti-CD3/anti-CD19 bispecific T-cell-engager) after R-CHOP bridging therapy for patients with RT.

Immune checkpoint inhibitors have been incorporated as the standard of care for some high-grade neuroendocrine neoplasms (NEN), but their efficacy in digestive NEN is still unclear. Here the authors report the results of a phase II trial of nivolumab (anti-PD1) in combination with platinum-doublet chemotherapy (carboplatin-etoposide) as first-line treatment in patients with unresectable or metastatic advanced grade 3 NENs of gastro-enteropancreatic or unknown origin.

Sacituzumab Govitecan, TROP-2 targeted antibody drug conjugate, is effective for the treatment of breast cancer, but its potential utility for the treatment of breast cancer brain metastasis and recurrent glioblastoma is unclear. Here, the authors present a window-of-opportunity phase 0 trial reporting the central nervous system penetrance and intracranial efficacy of Sacituzumab Govitecan.

Patritumab deruxtecan (HER3-DXd) is a promising therapy for breast cancer, targeting HER3. Here, the authors analyse the genomic factors that affect the response to HER3-DXd in patients with early-stage HER2-negative breast cancer as part of the SOLTI-1805 TOT-HER3 clinical trial and report outcomes for Part B of the trial using lower HER3-DXd dose in patients with HER2-negative breast cancer.

Locally advanced hypopharyngeal squamous cell carcinoma is an aggressive form of head and neck cancer with a poor prognosis. Here, the authors report the safety and efficacy of induction camrelizumab (anti-PD-1) and chemotherapy for the treatment of locally advanced hypopharyngeal squamous cell carcinoma.

Safety concerns limit the success of HER2-targeting antibody-drug conjugates (ADCs) for the treatment of HER2-postive breast cancer. Here, the authors present a phase 1a/b trial reporting the safety and preliminary efficacy of FS-1502, an anti-HER2 ADC with a cancer-selective cleavable linker, for the treatment of HER2-positive metastatic breast cancer.

Robotic surgery has been demonstrated to improve short-term outcomes for patients with gastric cancer who received a gastrectomy, but the long-term effects are less clear. Here, the authors report the survival outcomes of their phase 2 randomized controlled trial comparing robotic to laparoscopic distal gastrectomy in patients with resectable gastric cancer.

Recent studies show that targeting CXCL12 can improve the effect of radiotherapy (RT) in preclinical models of glioblastoma (GBM). Here, the authors report the safety and preliminary efficacy of a phase I/II clinical trial investigating an L-RNA aptamer-based CXCL12 inhibitor (NOX-A12) in combination with RT in patients with newly-diagnosed GBM.

Cibisatamab is a T-cell bispecific antibody targeting the carcinoembryonic antigen (CEA) on tumor cells and CD3 epsilon chain on T cells. Here the authors report the results of two clinical trials of cibisatamab as monotherapy (NCT02324257) and in combination with atezolizumab (anti-PD-L1; NCT02650713) in patients with CEA-positive solid tumors.

Autologous tumor lysate (ATL) dendritic cell (DC) vaccination can induce local and systemic anti-tumor immune responses in malignant glioma patients. In this randomized phase II clinical trial, the authors evaluate the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to ATL-DC vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas.

CAR-T cell therapies targeting BCMA have shown promising responses in patients with multiple myeloma (MM), however primary resistance and relapse are frequently observed. Here the authors report the results of a phase I//II study of bispecific CAR T-cells targeting BCMA and CD19 in relapsed/refractory MM.

Potential synergism between BTK inhibitor and lenalidomide in treating aggressive B-cell lymphoma has been suggested. Here, the authors report a single-arm phase II clinical trial of combination of acalabrutinib, lenalidomide and rituximab in patients with aggressive Relapsed/Refractory aggressive B-cell non-Hodgkin lymphoma.

ATR/CHK1 pathway inhibitors represent a therapeutic option for platinum-resistant high-grade serous ovarian carcinoma (HGSOC). Here the authors report the results of a phase 2 clinical study of the CHK1 inhibitor prexasertib in patients with BRCA wild-type platinum-resistant HGSOC with or without biopsiable disease.

Post-neoadjuvant treatment options for patients with triple-negative breast cancer (TNBC) include the chemo-drug capecitabine but also immune checkpoint inhibitors. Here the authors report the results of a phase II study of adjuvant nivolumab, capecitabine or the combination in patients with residual TNBC.

Intrinsic and acquired resistances to CDK4/6 inhibitors have been described in patients with breast cancer. Here the authors report the results from a phase I/II clinical trial of the aromatase inhibitor exemestane plus everolimus (mTOR inhibitor) and palbociclib (CDK4/6i) in patients with metastatic breast cancer, assessing safety, clinical efficacy, as well as genomic and transcriptomic determinants of resistance.

Bavituximab is a genetically engineered IgG1 chimeric antibody that targets phosphatidylserine. Here the authors report the results of a single-arm phase 2 trial of bavituximab in combination with pembrolizumab (anti-PD1) for patients with unresectable hepatocellular carcinoma.

Previously, the authors reported the primary analysis of a phase III randomized control trial investigating dual HER2 blockade in HER2-positive early/locally advanced breast cancer. Here, the authors report the long-term efficacy and safety analysis of this trial.

Prognosis for patients diagnosed with advanced stage ovarian cancer remains poor. Here the authors report the results of a phase 2 study of a triple combination of the PARP inhibitor olaparib in combination with durvalumab (anti-PD1) and bevacizumab (antiVEGF) in advanced ovarian cancer.

Alterations of therapeutic pressures have been shown to affect clonal evolution of resistance. Here, the authors conducted a single arm, phase 2 trial consisting of alternating osimertinib and gefitinib in non-small cell lung cancer, and found ctDNA dynamics were predictive of response.

Immunotherapy using dendritic cell (DC)-based vaccination has been exploited in the clinic for cancer treatment. Here the authors report the results of a randomized, placebo-controlled, phase 3 trial of adjuvant blood-derived DC cell-based therapy in patients with stage IIIB and IIIC melanoma.

CAMILLA is a basket trial evaluating cabozantinib plus the ICI durvalumab in chemorefractory gastrointestinal cancer. Here, the authors present the result of the phase II in the colorectal cohort.

Combining standard 4-6 cycles of chemotherapy with immune checkpoints inhibitors has shown to improve survival in patients with non-small cell lung cancer (NSCLC), however increased toxicities have also been reported. Here the authors report the results of a phase 2 trial of sintilimab (anti-PD1) with two cycles of chemotherapy for treatment of previously untreated advanced squamous NSCLC.

Recent work indicates that drug delivery to the brain can be improved through disruption of the blood brain barrier using low intensity pulsed ultrasound. Here, the authors report a phase I/II clinical trial investigating the combination of a nine-emitter implantable ultrasound device and carboplatin in patients with recurrent glioblastoma.

Immunotherapy with immune checkpoint inhibitors and targeted therapy with BRAF and MEK inhibition have revolutionized the treatment of melanoma. Here the authors report the results of a phase II trial of neoadjuvant cobimetinib (MEK inhibitor) and atezolizumab (anti-PD-L1) with or without the BRAF inhibitor vemurafenib in patients with resectable Stage III melanoma.

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Here the authors report the results of a phase II clinical trial of camrelizumab (anti-PD1) and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma.

KN046 is a recombinant anti-PD-L1/CTLA-4 bispecific antibody that has shown clinical activity in different advanced solid tumors. Here the authors report the results of a phase II study of KN046 in combination with nab-paclitaxel as first-line treatment of metastatic triple-negative breast cancer.

Preclinical studies have suggested the synergistic effect of epigenetic modulators and immunotherapy. Here the authors report the results of a phase Ib/II trial of durvalumab and guadecitabine in advanced clear cell renal cell carcinoma.

Although most patients achieve complete response after standard-of-care treatment, residual disease in patients with nasopharyngeal carcinoma is associated with poor prognosis. Here the authors report the results of a phase 2 trial of toripalimab (anti-PD1) plus capecitabine for patients with residual nasopharyngeal carcinoma.

Response rates to immune-checkpoint inhibitors in patients with advanced sarcoma remain modest. Here the authors report the results of a phase 2 study of durvalumab (anti-PD-L1) in combination with the anti-VEGF receptor tyrosine-kinase inhibitor pazopanib in unselected advanced sarcomas with correlative genomic analysis.

SECOMBIT was a clinical trial testing different sequences of immunotherapy (ipilimumab plus nivolumab) and targeted therapy (encorafenib plus binimetinib) for untreated BRAF-mutated metastatic melanoma. Here the authors report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy, and preliminary biomarkers evaluation.

Bipolar androgen therapy (BAT) is a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Here the authors report the results of a phase 2 trial of BAT plus nivolumab (anti-PD1) in patients with advanced mCRPC.

Neoadjuvant treatment represents a therapeutic option for locally advanced gastric cancer (LAGC). Here the authors report the results of a randomized phase 2 trial of camrelizumab (anti-PD1) and apatinib (anti-VEGFR2) combined with nab-paclitaxel plus S-1 versus chemotherapy alone as neoadjuvant treatment for LAGC.

Oncolytic measles virus (MV) vaccine strains have shown preclinical antitumor activity against glioblastoma (GBM). Here the authors report the results of a phase 1 trial of intratumoral administration of a MV strain engineered to express the carcinoembryonic antigen in patients with recurrent GBM including assessment of viral replication and proinflammatory remodeling of the treated tumors.

Antibody drug conjugates (ADCs) with pyrrolobenzodiazepine (PBD) payloads are promising cancer therapeutics but are limited by toxicity. Here, the authors develop a HER2-targeted ADC (DHES0815A) with a reduced potency PBD payload that demonstrated promising preclinical efficacy and nonhuman primate tolerability, but culminated in a phase I clinical trial in patients with metastatic breast cancer which was terminated due to toxicity.

This phase I/II clinical trial was designed to assess safety and efficacy of gene therapy for Bothnia dystrophy, an inherited retinal degeneration leading to blindness. Kvanta et al. show interim results from 12 patients with meaningfully improved visual function in dim light.

This randomized trial assessed the effectiveness and safety of single blastocyst transfer vs single cleavage-stage embryo transfer among women with good prognosis. Here, the authors show improved cumulative live birth rates and relatively unfavorable perinatal outcomes after blastocyst transfer.

Bimodal neuromodulation combining sound therapy with electrical tongue stimulation using the Lenire device is a nonsurgical treatment for tinnitus. Here, the authors show the positive efficacy and safety results of a controlled one-arm pivotal trial that led to FDA De Novo approval of the Lenire device.

Individuals with type 1 diabetes face challenges in determining the insulin doses they need before high-fat meals and meals followed by aerobic exercises. Here, the authors show that it is clinically feasible to automatically determine these insulin doses for each individual using a reinforcement learning algorithm.

Here, in, the authors investigate the relationship between fecal microbiota and nutritional status in a trial on 380 Cambodian schoolchildren, establishing a correlation between micronutrient deficiencies and microbiota profiles.

A regulated stress response is essential for healthy child growth and development. Here, the authors show that a nutrition, water, sanitation, and hygiene intervention enhanced adaptive responses of the physiological stress system in early childhood.

Viral infection is a common risk for immune-compromised individuals, particularly pediatric patients receiving hematopoietic stem cell transplants. Here the authors report a phase II trial testing adoptive transfer of third party, virus-specific T cells on the feasibility, safety, clinical responses, as well as homeostasis of antiviral immunity in the recipients.

Childhood malnutrition in Africa is a glaring example of global inequality, and mortality remains high. Here, the authors report the results of the TAME randomized phase II clinical trial, in which intestinal healing was the target of four potential interventions in malnourished children in Zambia and Zimbabwe.

In the CELLTOP Phase I trial, stem cells were harvested from patients with spinal cord injury and injected into their central nervous system after processing. The procedure was safe, with no reported serious adverse events during the 2-year follow-up period.

Pharmacological inhibition of gamma-secretase induced partial recovery of hearing in animal models. Here, the authors present the safety and efficacy results and key learnings of the First in Human Phase I/IIa study of a gamma-secretase inhibitor in patients with acquired Hearing Loss.

Here, the authors present the results of the PROMOTe trial, reporting improved cognition with prebiotic vs placebo in twins over 60 years old, probing that remote trials are feasible in older adults, and suggesting that the gut microbiota may represent a therapeutic target for age-associated morbidity.

Post-stroke walking impairment is a significant public health concern. Here, the authors perform an interventional, randomized controlled trial evaluating the efficacy and safety of InTandem™, an autonomous neurorehabilitation system utilizing auditory-motor entrainment to improve walking after stroke.

Invariant natural killer T (iNKT) cells recognize abnormal cells, but their T cell receptor is not variable and kill cancerous or infected target cells without MHC I restriction. Here, the authors show that in a clinical trial, donor-unrestricted allogeneic iNKT cells could be safely administered to human COVID-19 patients suffering from acute respiratory distress syndrome and trigger an anti-inflammatory response.

A personalized letter from the Medical Examiner-Coroner in Los Angeles County has proven effective at reducing opioid and benzodiazepine prescribing. Here the authors show that the introduction of if/when-then planning prompts in to the letter further reduced opioid prescribing by 12.85% and benzodiazepine prescribing by 8.32%; they were most effective for clinicians with multiple patient deaths due to accidental opioid-related overdose.

Diabetic retinopathy is a complication of diabetes that can be prevented through screening, yet adherence is low. Here, the authors show that autonomous AI increases diabetic eye exam completion in a diverse cohort of youth with diabetes.

Functional dyspepsia (FD) is a common chronic gastrointestinal disorder. Here, in a randomized, parallel-group, positive-drug, and placebo-controlled clinical trial, the authors show that supplementation with the probiotic Bifidobacterium animalis subsp. lactis BL-99 (BL-99) improves FD clinical response rate and promotes accumulation of SCFA-producing microbiota.

Oral nicotinamide riboside (NR) at a dose of 3000 mg daily for 30 days is safe and associated with a pronounced systemic augmentation of the NAD metabolome, but no methyl donor depletion.

The faster a drug enters the brain, the greater its addictive potential. Using simultaneous PET-fMRI in humans, here the authors report a neural circuit responding to fast but not slow dopamine increases from intravenous versus oral methylphenidate delivery.

The authors report data from a Phase IIa randomised, double-blind trial in patients with NASH showing that BI 1467335 strongly and dose-dependently inhibited AOC3 activity (involved in hepatic inflammation) and was well tolerated at all tested doses.

Non-alcoholic fatty liver disease is a growing health burden with limited treatment options worldwide. Herein the authors report a randomized, double-blind, placebo-controlled, multiple-dose trial of a first-in-class pan-phosphodiesterase inhibitor ZSP1601 in NAFLD patients.

Genotype patterns may modify diet effects on weight loss, with greater weight loss on genotype-concordant diets. Here, the authors show that with the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater weight loss on genotype-concordant diets.

Neuroinflammation and autophagy are two pillars of ALS pathogenesis targeted by rapamycin. Here, in a randomized, double-blind, phase 2 clinical trial, the authors find rapamycin to be safe and well tolerated in ALS patients, supporting further studies.

A beneficial effect of parasitic worms on metabolic health has been postulated based on epidemiological and animal studies. Here, the authors show in a phase I clinical trial that treatment of people at risk of type 2 diabetes with hookworms is safe and may improve key measures of metabolic health.

Different classes of biologic therapeutics have been assessed in the context of Vogt-Koyanagi-Harada disease. Here the authors compared cyclosporine immunosuppression or adalimumab in a randomised clinical trial for the treatment of patients with Vogt-Koyanagi-Harada disease and found non-inferiority upon treatment with cyclosporine.

Using data from a phase 3 efficacy trial, the authors here show that post-boost Omicron BA.1 spike-specific binding and neutralizing antibodies inversely correlate with Omicron COVID-19 and booster efficacy for naive and non-naive participants, supporting the continued use of antibody as a surrogate endpoint.

Building on evidence from the phase 3 COVE trial, the authors report the long-term safety and effectiveness of primary vaccination and boosting with mRNA-1273 against COVID-19, including during emergent variant waves.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

Here, the authors report the results of a randomised trial assessing whether adding multiplex real-time PCR to conventional testing reduces antibiotic use in community-acquired pneumonia and observe no significant reduction in days of antibiotic therapy or in 30-day mortality.

As part of a randomized controlled trial in Viet Nam, this study finds that pneumococcal-specific memory B cells (B_mem) are higher following a 1 + 1 compared to a 0 + 1 pneumococcal conjugate vaccine (PCV) schedule and higher for PCV13 compared to PCV10. B_mem did not wane as rapidly as IgG by 24 months of age.

In this randomized, double-blind, placebo-controlled trial young adults with chronic diarrhea were randomized into treatment and placebo groups to evaluate the effects of the probiotic Lactiplantibacillus plantarum P9 strain administraiton. The primary endpoint was the diarrhea symptom severity score. Both intention-to-treat and per-protocol analyses reveal a modest yet statistically significant reduction in diarrhea severity.

In this randomized, placebo-controlled phase 3 clinical trial, the authors assess efficacy, immunogenicity, and safety of the inactivated SARS-CoV-2 vaccine CoronaVac in children and adolescents aged 6 months to 17 years. The study was carried out in Chile, South Africa, Malaysia, and the Philippines, and coincided with the emergence of the Omicron variant.

In this phase IV trial, the authors assessed antibody responses to multiple vaccines in the same individuals of different age groups and show that the responsiveness to different vaccines was highly variable but that a small group of older male adults responded low to multiple vaccines.

Reviewer recognition:

Here, the authors report results from a randomized, placebo-controlled phase 3 trial of the tetravalent SARS-CoV-2 protein vaccine SCTV01E, demonstrating a favorable efficacy profile during a time when predominant viral variants were changing from BA.5 and BF.7 to XBB.

In this randomized, controlled integrated phase 1/2/3a/3b clinical trial, the authors show that the self-amplifying mRNA COVID-19 vaccine ARCT-154 shows good immunogenicity and is safe and efficient against COVID-19 (57% against any COVID-19, and 95% against severe COVID-19).

In this clinical trial, the authors show that a 5-day molnupiravir treatment reduces SARS-CoV-2 viral load in at-risk outpatients by day 5 but mostly fails to clear virus, leads to lower spike antibody response by day 14 and higher virus mutation rates.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Using longitudinal profiling of 6385 plasma proteins in hospitalised patients, the authors demonstrate that alveolar capillary barrier disruption in critical COVID-19 is reflected in the plasma proteome, and is attenuated with imatinib treatment.

Here the authors report an exploratory analysis of a clinical trial that tested different influenza virus vaccination platforms. The results show that multiple seasons of recombinant or cell-based influenza vaccinations may be needed to redirect antibody responses away from immune memory to egg-adapted epitopes and refocus on epitopes on the circulating viruses.

Here, Heitmann et al. report results from a Phase I/II trial evaluating CoVac-1, a peptide-based T-cell activator, in patients with B-cell deficiency, demonstrating potent induction of SARS-CoV-2-specific T-cell responses along with a favorable safety profile.

Here the authors provide safety and immunogenicity data for an AdV5-based SARS-CoV-2 vaccine, administered intramuscularly as heterologous booster after three-doses of inactivated SARS-CoV-2 vaccine in Chinese adults.

Here the authors show in a phase 1 trial that a recombinant subunit vaccine based on the gamma variant of SARS-CoV-2 exhibits a satisfactory safety profile, and induces a broad booster response of neutralizing antibodies and a booster effect on T cell immunity in individuals previously immunized with different SARS-CoV-2 vaccine platforms.

Here the authors report initial findings of a phase 1 clinical trial, showing that an investigational, mRNA-based vaccine for seasonal influenza (mRNA-1010) has no safety concerns and produces immune responses in adults that are similar or higher than a licensed comparator vaccine.

Palmer et al. present interim findings from their clinical trial; they describe the reactogenicity and immunogenicity results of a self-amplifying mRNA SARS-CoV-2 booster vaccine within an older population (≥60 years of age).

Authors study antibody responses elicited against Omicron BA.1 and variants, by Omicron BA.1-bivalent mRNA-1273.214 vaccine compared with mRNA-1273 vaccination, when administered as a second booster, 90 days post-administration.