SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial.

BACKGROUND: A self-assembling SARS-CoV-2 WA-1 recombinant spike ferritin nanoparticle (SpFN) vaccine co-formulated with Army Liposomal Formulation (ALFQ) adjuvant containing monophosphoryl lipid A and QS-21 (SpFN/ALFQ) has shown protective efficacy in animal challenge models. This trial aims to assess the safety and immunogenicity of SpFN/ALFQ in a first-in-human clinical trial. METHODS: In this phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial, adults were randomly assigned (5:5:2) to receive 25 µg or 50 µg of SpFN/ALFQ or saline placebo intramuscularly at day 1 and day 29, with an optional open-label third vaccination at day 181. Enrolment and randomisation occurred sequentially by group; randomisation was done by an interactive web-based randomisation system and only designated unmasked study personnel had access to the randomisation code. Adults were required to be seronegative and unvaccinated for inclusion. Local and systemic reactogenicity, adverse events, binding and neutralising antibodies, and antigen-specific T-cell responses were quantified. For safety analyses, exact 95% Clopper-Pearson CIs for the probability of any incidence of an unsolicited adverse event was computed for each group. For immunogenicity results, CIs for binary variables were computed using the exact Clopper-Pearson methodology, while CIs for geometric mean titres were based on 10 000 empirical bootstrap samples. Post-hoc, paired one-sample t tests were used to assess the increase in mean log-10 neutralising antibody titres between day 29 and day 43 (after the second vaccination) for the primary SARS-CoV-2 targets of interest. This trial is registered at ClinicalTrials.gov, NCT04784767, and is closed to new participants. FINDINGS: Between April 7, and June 29, 2021, 29 participants were enrolled in the study. 20 individuals were assigned to receive 25 µg SpFN/ALFQ, four to 50 µg SpFN/ALFQ, and five to placebo. Neutralising antibody responses peaked at day 43, 2 weeks after the second dose. Neutralisation activity against multiple omicron subvariants decayed more slowly than against the D614G or beta variants until 5 months after second vaccination for both dose groups. CD4+ T-cell responses were elicited 4 weeks after the first dose and were boosted after a second dose of SpFN/ALFQ for both dose groups. Neutralising antibody titres against early omicron subvariants and clade 1 sarbecoviruses were detectable after two immunisations and peaked after the third immunisation for both dose groups. Neutralising antibody titres against XBB.1.5 were detected after three vaccinations. Passive IgG transfer from vaccinated volunteers into Syrian golden hamsters controlled replication of SARS-CoV-1 after challenge. INTERPRETATION: SpFN/ALFQ was well tolerated and elicited robust and durable binding antibody and neutralising antibody titres against a broad panel of SARS-CoV-2 variants and other sarbecoviruses. FUNDING: US Department of Defense, Defense Health Agency.

Safety and immunogenicity of Multimeric-001 (M-001) followed by seasonal quadrivalent inactivated influenza vaccine in young adults - A randomized clinical trial.

BACKGROUND: The continuing evolution of influenza viruses poses a challenge to vaccine prevention, highlighting the need for a universal influenza vaccine. We evaluated the safety and immunogenicity of one such candidate, Multimeric-001 (M-001), when used as a priming vaccine prior to administration of quadrivalent inactivated influenza vaccine (IIV4). METHODS: Healthy adults 18 to 49 years of age were enrolled in a phase 2 randomized, double-blind placebo-controlled trial. Participants received two doses of either 1.0-mg M-001 or saline placebo (60 per study arm) on Days 1 and 22 followed by a single dose of IIV4 on about Day 172. Safety, reactogenicity, cellular immune responses and influenza hemagglutination inhibition (HAI) and microneutralization (MN) were assessed. RESULTS: The M-001 vaccine was safe and had an acceptable reactogenicity profile. Injection site tenderness (39% post-dose 1, 29% post-dose 2) was the most common reaction after M-001 administration. Polyfunctional CD4+ T cell responses (perforin-negative, CD107α-negative, TNF-α+, IFN-γ+, with or without IL-2) to the pool of M-001 peptides increased significantly from baseline to two weeks after the second dose of M-001, and this increase persisted through Day 172. However, there was no enhancement of HAI or MN antibody responses among M-001 recipients following IIV4 administration. CONCLUSIONS: M-001 administration induced a subset of polyfunctional CD4+ T cells that persisted through 6 months of follow-up, but it did not improve HAI or MN antibody responses to IIV4. (clinicaltrials.gov NCT03058692).

Safety and Immunogenicity of Influenza A/H5N8 Virus Vaccine in Healthy Adults: Durability and Cross-reactivity of Antibody Responses.

BACKGROUND: Influenza A/H5N8 viruses infect poultry and wild birds in many countries. In 2021, the first human A/H5N8 cases were reported. METHODS: We conducted a phase I, cohort-randomized, double-blind, controlled trial of inactivated influenza A/H5N8 vaccine (clade 2.3.4.4c) administered with or without adjuvant. Cohort 1 subjects received either two doses of AS03-adjuvanted vaccine containing 3.75 µg or 15 µg hemagglutinin (HA); two doses of 15 µg HA unadjuvanted vaccine; or one dose of AS03-adjuvanted vaccine (3.75 µg or 15 µg HA), followed by one dose of non-adjuvanted vaccine (same HA content). Cohort 2 subjects received two doses of MF59-adjuvanted vaccine containing 3.75 µg or 15 µg HA, or 15 µg HA of non-adjuvanted vaccine. Subjects were followed for 13 months for safety and immunogenicity. RESULTS: We enrolled 386 adult subjects in good health. Solicited adverse events were generally mild and more common among subjects who received adjuvanted vaccines. Antibody responses (hemagglutination inhibition or microneutralization assays) were highest in the two-dose AS03 group, followed by the one-dose AS03 group, the MF59 groups, and the non-adjuvanted groups. Antibody levels returned to baseline 12 months after the second vaccination in all groups except the 15 µg AS03-adjuvanted group. Cross-reactive antibodies to clade 2.3.4.4b strains isolated from recent human cases were demonstrated in a subset of both 15 µg adjuvanted groups. CONCLUSIONS: Two doses of influenza A/H5N8 vaccine were well-tolerated. Immunogenicity improved with receipt of two doses of adjuvanted vaccine and higher antigen content. (Funded by the National Institute of Allergy and Infectious Diseases.

A Multicenter, Controlled Human Infection Study of Influenza A(H1N1)pdm09 in Healthy Adults.

BACKGROUND: We evaluated the associations between baseline influenza virus-specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza virus infection in a controlled human infection study. METHODS: We inoculated unvaccinated healthy adults aged 18-49 years with an influenza A/California/04/2009/H1N1pdm-like virus (NCT04044352). We collected serial safety labs, serum for HAI and MN, and nasopharyngeal swabs for reverse-transcription polymerase chain reaction (RT-PCR) testing. Analyses used the putative seroprotective titer of ≥40 for HAI and MN. The primary clinical outcome was mild-to-moderate influenza disease (MMID), defined as ≥1 postchallenge positive qualitative RT-PCR test with a qualifying symptom/clinical finding. RESULTS: Of 76 participants given influenza virus challenge, 54 (71.1%) experienced MMID. Clinical illness was generally very mild. MMID attack rates among participants with baseline titers ≥40 by HAI and MN were 64.9% and 67.9%, respectively, while MMID attack rates among participants with baseline titers <40 by HAI and MN were 76.9% and 78.3%, respectively. The estimated odds of developing MMID decreased by 19% (odds ratio, 0.81 [95% confidence interval, .62-1.06]; P = .126) for every 2-fold increase in baseline HAI. There were no significant adverse events. CONCLUSIONS: We achieved a 71.1% attack rate of MMID. High baseline HAI and MN were associated with protection from illness. Clinical Trials Registration. NCT04044352.

Neutralizing Antibody Kinetics and Immune Protection Against Herpes Simplex Virus 1 Genital Disease in Vaccinated Women.

BACKGROUND: Previously, our group conducted the Herpevac Trial for Women, a randomized efficacy field trial of type 2 glycoprotein D (gD2) herpes simplex virus (HSV) vaccine adjuvanted with ASO4 in 8323 women. Study participants were selected to be seronegative for HSV-1 and HSV-2. We found that the vaccine was 82% protective against culture-positive HSV-1 genital disease but offered no significant protection against HSV-2 genital disease. Efficacy against HSV-1 was associated with higher levels of antibody to gD2 at enzyme-linked immunosorbent assay (ELISA). METHODS: To better understand the results of the efficacy study, we measured postvaccination concentrations of neutralizing antibody (nAb) to either HSV-1 and HSV-2 from HSV-infected study participants and matched uninfected controls. Statistical modeling was used to determine whether these responses were correlated with protection against HSV. RESULTS: nAbs to either HSV-1 or HSV-2 were correlated with ELISA binding antibodies to gD2. HSV-1 or HSV-2 nAb findings support the observation of protection by higher levels of antibody against HSV-1 infection, but the lack of protection against HSV-2 remains unexplained. CONCLUSIONS: The protection against HSV-1 infection observed in the Herpevac Trial for Women was associated with nAbs directed against the virus, although the power to assess this was lower in the nAb study compared with the ELISA results owing to smaller sample size. CLINICAL TRIALS REGISTRATION: NCT00057330.

Plant-based meats in China: a cross-sectional study of attitudes and behaviours.

BACKGROUND: This study investigated potential opportunities or challenges for plant-based meat in the Chinese market. A quantitative framework was applied to determine the current level of familiarity and experience with plant-based meat among Chinese consumers, the proportion of consumers who would try or purchase plant-based meat, which demographics within China are most likely to buy plant-based meat and which attitudes are important in driving the purchase intent of plant-based meat. METHODS: A pre-registered cross-sectional online survey (N = 1206) was distributed to respondents (matched to China's adult population for gender and age). RESULTS: Respondents reported a variety of dietary identities, with 43.4% reporting that they were reducing or avoiding meat. The majority of respondents (60.1%) said they had eaten plant-based meat at least once before. Of those who said they had never eaten plant-based meat, 41.9% intended to try it and 31.4% intended to purchase it. The strongest attitudinal predictor of plant-based meat purchase intent was perceived healthiness (ß = 0.235, p < 0.001), whereas the strongest demographic predictor of plant-based meat purchase intent was age (ß = -0.248, p < 0.001). CONCLUSIONS: The findings of this study suggest that an approach based on increasing opportunities for trial, as well as appealing to specific attitudinal and demographic predictors of plant-based purchase intent, could prove successful in increasing adoption of plant-based and alternative meat products.

Nomenclature of cell-cultivated meat & seafood products.

Cell-cultivated meat and seafood is getting closer to a reality for consumers in the US and around the world. However, regulators are still largely lagging behind on regulating production and labelling of these products. In a large experimental study using a representative US sample (N = 2653), we tested 9 different names for 3 different types of meat and seafood products in terms of their clarity, consumer appeal, and communication of safety and allergenicity. We found that terms proposed by the conventional meat and seafood industry including 'artificial' and 'lab-grown' tended to score low in terms of consumer appeal, purchase intent, and perceived safety, while 'artificial' also had the lowest score on clarity and communicating allergenicity. On the other hand, terms proposed by the cell-cultivated industry including 'Novari' scored high in terms of appeal and purchase intent but scored low in terms of clarity. The terms 'cell-cultured' and 'cell-cultivated' were the best all round labels in terms of clarity, appeal, and communicating safety and allergenicity - in particular, the addition of the prefix 'cell-' increased understanding compared to 'cultured' or 'cultivated' labels. The most-understood label was a short descriptive phrase ('grown from [animal] cells, not farmed [or fished]'), suggesting that additional wording on packaging could aid consumer understanding in this early stage. A high proportion of consumers were uncertain about the allergen status of cell-cultivated products under all names, suggesting that cell-cultivated products should be labelled as the type of meat they are, and carry applicable allergen information.

Discovering cell-active BCL6 inhibitors: effectively combining biochemical HTS with multiple biophysical techniques, X-ray crystallography and cell-based assays.

By suppressing gene transcription through the recruitment of corepressor proteins, B-cell lymphoma 6 (BCL6) protein controls a transcriptional network required for the formation and maintenance of B-cell germinal centres. As BCL6 deregulation is implicated in the development of Diffuse Large B-Cell Lymphoma, we sought to discover novel small molecule inhibitors that disrupt the BCL6-corepressor protein-protein interaction (PPI). Here we report our hit finding and compound optimisation strategies, which provide insight into the multi-faceted orthogonal approaches that are needed to tackle this challenging PPI with small molecule inhibitors. Using a 1536-well plate fluorescence polarisation high throughput screen we identified multiple hit series, which were followed up by hit confirmation using a thermal shift assay, surface plasmon resonance and ligand-observed NMR. We determined X-ray structures of BCL6 bound to compounds from nine different series, enabling a structure-based drug design approach to improve their weak biochemical potency. We developed a time-resolved fluorescence energy transfer biochemical assay and a nano bioluminescence resonance energy transfer cellular assay to monitor cellular activity during compound optimisation. This workflow led to the discovery of novel inhibitors with respective biochemical and cellular potencies (IC50s) in the sub-micromolar and low micromolar range.

Emerging trends in the agri-food sector: Digitalisation and shift to plant-based diets.

Our planet is currently facing unprecedented interconnected environmental, societal, and economic dilemmas due to climate change, the outbreak of pandemics and wars, among others. These global challenges pose direct threats to food security and safety and clearly show the urgent need for innovative scientific solutions and technological approaches. Backed by the current alarming situation, many food-related trends have emerged in recent years in response to these global issues. This review looks at two megatrends in agriculture and the food industry; the shift to vegetable diets and the digital transformation in food production and consumption patterns. On one side, several innovative technologies and protein sources have been associated with more sustainable food systems and enhanced nutritional quality and safety. On the other side, many digital advanced technologies (e.g., artificial intelligence, big data, the Internet of Things, blockchain, and 3D printing) have been increasingly applied in smart farms and smart food factories to improve food system outcomes. Increasing adoption of vegetal innovations and harnessing Industry 4.0 technologies along the food supply chain have the potential to enable efficient digital and ecological transitions.

Clinical signs and symptoms associated with acute HIV infection from an intensely monitored cohort on 2 continents.

ABSTRACT: Define the clinical presentation of acute human immunodeficiency virus infection (AHI) among men and women from 2 continents to create a clinical scoring algorithm.Comparison of incident sign and symptom between those with and without AHI.At-risk human immunodeficiency virus (HIV) negative men and women in Thailand, Kenya, Tanzania, and Uganda underwent twice-weekly testing for HIV. Newly diagnosed participants were evaluated twice weekly for 21 days after infection.Of the 3345 participants enrolled, 56 African females and 36 biological males from Thailand were diagnosed with AHI. Four hundred fifty-two of their encounters were compared to 18,281 HIV negative encounters. Due to a high degree of heterogeneity among incident symptoms, 2 unique subgroups based upon geography and sex were created. Among Thai males, the signs and symptoms with the greatest odds ratio (OR) between AHI and uninfected participants were nausea (OR 16.0, 95% confidence interval [CI] 3.9-60.2, P < .001) and lymphatic abnormalities (OR 11.8, 95% CI 4.2-49.0, P < .001); and among African females were pain behind the eyes (OR 44.4, 95% CI 12.0-158.0, P < .0001) and fatigue (OR 22.7, 95% CI 11.3-44.3, P < .001). The Thai male scoring algorithm had a 66% sensitivity and 84% specificity while the African female algorithm had a sensitivity of 27% and specificity of 98%.The different incident symptoms during AHI necessitated creating 2 different scoring algorithms that can guide diagnostic testing among a particular sex in the appropriate geographic setting. Further research on risk exposure, sex, and demographic specific models is warranted.

COVID-19 pandemic: rapid survey on social and mobility impact in Algerian cities.

Aims: The impacts of the COVID-19 pandemic were very significant on the population following the application of total and partial confinement measures. Our study aimed to investigate the social and mobility impact of confinement on the Algerian population using a cross-sectional survey launched after 3 days of the start of confinement to quickly assess the impacts during the period of March 23 to April 12, 2020. Subject and methods: We used an online questionnaire to obtain 678 responses from internet users, who were living in confinement in Algeria. According to the gender variable, our sample included 405 men (59.7%) and 273 women (40.3%). Results: The statistical analysis performed showed that road interactions and mobility are only part of the social interactions, and that 95.1% of the respondents avoided family visits during these first 3 weeks of confinement. Of respondents, 85.5% spend a considerable amount of time chatting with family, 66.6% found the diet beneficial during this period, 57% participated in sports to preserve their health, 87.2% of respondents respected the travel ban, only 20.2% of those surveyed used a bicycle for travel, and 55.9% traveled on foot to go shopping. Conclusion: The study also showed significant impacts on the social aspects linked to travel, namely family relationships and sports activities, as well as significant impacts on the mobility of people.

Going veggie: Identifying and overcoming the social and psychological barriers to veganism.

We conceptualize the journey to ethical veganism in the stages of the transtheoretical model of change, from precontemplation through contemplation, preparation, action, and maintenance. At each stage, we explore the psychological barriers to progressing towards veganism, discuss how they manifest, and explore ways to overcome them. It is hoped that this paper can be used as a guide for animal advocates to identify the stage an individual is at, and understand and overcome the social and psychological barriers they may face to progressing. We argue that, while many people are ignorant of the cruel practices entailed in animal farming, many deliberately avoid thinking about the issue, are unable to appreciate the scale of the issue, and simply tend to favour the status quo. When engaging with the issue of farm animal suffering, meat-eaters are largely driven by cognitive dissonance, which manifests as motivated reasoning aimed at protecting one's image of oneself and one's society. This is facilitated by confirmation bias and complicit media which cater to the preferred views of their meat-eating audience. Even once convinced of veganism, habit and willpower present further barriers to acting on those beliefs. This is all in the context of a speciesist and carnistic culture where meat consumption is normal, farming is noble, and vegans are 'others'. We locate and elucidate each of these biases within the stages of the transtheoretical model and discuss the implications of this model for animal advocates and for further research.

The farmers' dilemma: Meat, means, and morality.

Evidence overwhelmingly supports the view that we need to drastically reduce our consumption of animal products for reasons related to the environment and public health, while moral concerns about the treatment of animals in agriculture are becoming ever more common. As governments increasingly recognize the need to change our food production and alternative protein products become more appealing to consumers, agriculture finds itself in a unique period of transition. How do farmers respond to the changing atmosphere? We present secondary analyses of qualitative and quantitative data to highlight some of the uncertainty and ambivalence about meat production felt throughout the farming community. Survey data from France and Germany reveals that in both countries, those who work in the meat industry have significantly higher rates of meat avoidance than those who do not work in the industry. While non-meat-industry workers are more likely to cite concerns for animals or the environment, meat industry workers more often cite concerns about the healthiness or safety of the products. Concurrently, interviews with people who raise animals for a living suggest that moral concerns among farmers are growing but largely remain hidden; talking about them openly was felt as a form of betrayal. We discuss these findings in the context of the ongoing agricultural transition, observe how tension has manifested as polarization among Dutch farmers, and offer some thoughts about the role of farmers in a new world of alternative proteins.

US and UK Consumer Adoption of Cultivated Meat: A Segmentation Study.

Despite growing evidence of the environmental and public health threats posed by today's intensive animal production, consumers in the west remain largely attached to meat. Cultivated meat offers a way to grow meat directly from cells, circumventing these issues as well as the use of animals altogether. The aim of this study was to assess the overall consumer markets and a range of preferences around cultivated meat in the US and the UK relating to nomenclature, genetic modification, health enhancements, and other features. To this end, we recruited large representative samples to participate in an online survey about cultivated meat, and subsequently analyzed segments (a) in the early majority population (guided by the Diffusion of Innovations Model), (b) by generation, and (c) in the general population. Our findings showed a high level of openness (80%) in both the US and UK populations, with 40% somewhat or moderately likely to try and 40% highly likely to try. Younger generations had the greatest openness: 88% of Gen Z, 85% of Millennials, 77% of Gen X, and 72% of Baby Boomers were at least somewhat open to trying cultivated meat. All segments envisioned cultivated meat to be nearly half of their total meat intake. Findings show that consumers prefer the terms 'cultured' and 'cultivated' over 'cell-based' and 'cell-cultured' for use in a social context and on packages, even though they perceive these terms as less descriptive. The most important on-package label was one indicating government assurances, and participants preferred non-GM products over GM products. We also found that US consumers prefer nutritionally superior meat over nutritionally equivalent meat. We discuss implications for product development, messaging, and understanding the likely adoption path of this food innovation.

Alternative proteins, evolving attitudes: Comparing consumer attitudes to plant-based and cultured meat in Belgium in two consecutive years.

Alternatives to conventional meat are considered an increasingly important tool in the drive to reduce consumption of animal products for environmental, public health and ethical reasons. We present two waves of a cross-sectional survey from a nationally representative sample in Belgium in 2019 (n = 1001) and 2020 (n = 1000). Participants answered questions online about their diets, attitudes towards existing plant-based meat alternatives, and attitudes towards cultured meat (grown from animal cells). We find that the proportion of Belgian consumers who said existing plant-based meat alternatives met their needs increased significantly from 44% in 2019 to 51% in 2020. We also find a significant increase in concern for issues related to animal agriculture, in particular the environment. We found no significant change in attitudes towards cultured meat between the two waves; in both 2019 and 2020, 39.3% of Belgian consumers said they would buy cultured meat. Regression analyses revealed that plant-based alternatives were more appealing to women and those with vegetarian diets, whilst cultured meat was more appealing to men. Overall, just 11.2% of consumers are both unsatisfied with existing meat alternatives and unwilling to buy cultured meat, while 43.2% of respondents were positive towards either plant-based or cultured meat, but not both, highlighting the need for a variety of alternative proteins in the market. Both cultured meat and plant-based meat were more appealing to younger consumers and those in the northern, predominantly Dutch-speaking region of Flanders. We discuss the implications of these findings for researchers and those seeking to strategically displace demand for animal products.

Selection of Oncogenic Mutant Clones in Normal Human Skin Varies with Body Site.

Skin cancer risk varies substantially across the body, yet how this relates to the mutations found in normal skin is unknown. Here we mapped mutant clones in skin from high- and low-risk sites. The density of mutations varied by location. The prevalence of NOTCH1 and FAT1 mutations in forearm, trunk, and leg skin was similar to that in keratinocyte cancers. Most mutations were caused by ultraviolet light, but mutational signature analysis suggested differences in DNA-repair processes between sites. Eleven mutant genes were under positive selection, with TP53 preferentially selected in the head and FAT1 in the leg. Fine-scale mapping revealed 10% of clones had copy-number alterations. Analysis of hair follicles showed mutations in the upper follicle resembled adjacent skin, but the lower follicle was sparsely mutated. Normal skin is a dense patchwork of mutant clones arising from competitive selection that varies by location. SIGNIFICANCE: Mapping mutant clones across the body reveals normal skin is a dense patchwork of mutant cells. The variation in cancer risk between sites substantially exceeds that in mutant clone density. More generally, mutant genes cannot be assigned as cancer drivers until their prevalence in normal tissue is known.See related commentary by De Dominici and DeGregori, p. 227.This article is highlighted in the In This Issue feature, p. 211.

Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge.

To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, a prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or a novel liposomal monophosphoryl lipid A (MPLA) formulation adsorbed to alum, ALFA. Binding antibody responses were robust and comparable between arms, while antibody-dependent neutrophil and monocyte phagocytotic responses were greatly enhanced by ALFA. Per-exposure vaccine efficacy against heterologous tier 2 SHIV mucosal challenge was 90% in ALFA-adjuvanted males (P = 0.002), while alum conferred no protection. Half of the ALFA-adjuvanted males remained uninfected after the full challenge series, which spanned seven months after the last vaccination. Antibody-dependent monocyte and neutrophil phagocytic responses both strongly correlated with protection. Significant sex differences in infection risk were observed, with much lower infection rates in females than males. In humans, MPLA-liposome-alum adjuvanted gp120 also increased HIV-1-specific phagocytic responses relative to alum. Thus, next-generation liposome-based adjuvants can drive vaccine elicited antibody effector activity towards potent phagocytic responses in both macaques and humans and these responses correlate with protection. Future protein vaccination strategies aiming to improve functional humoral responses may benefit from such adjuvants.

Modified Red Blue Vegetation Index for Chlorophyll Estimation and Yield Prediction of Maize from Visible Images Captured by UAV.

The vegetation index (VI) has been successfully used to monitor the growth and to predict the yield of agricultural crops. In this paper, a long-term observation was conducted for the yield prediction of maize using an unmanned aerial vehicle (UAV) and estimations of chlorophyll contents using SPAD-502. A new vegetation index termed as modified red blue VI (MRBVI) was developed to monitor the growth and to predict the yields of maize by establishing relationships between MRBVI- and SPAD-502-based chlorophyll contents. The coefficients of determination (R2s) were 0.462 and 0.570 in chlorophyll contents' estimations and yield predictions using MRBVI, and the results were relatively better than the results from the seven other commonly used VI approaches. All VIs during the different growth stages of maize were calculated and compared with the measured values of chlorophyll contents directly, and the relative error (RE) of MRBVI is the lowest at 0.355. Further, machine learning (ML) methods such as the backpropagation neural network model (BP), support vector machine (SVM), random forest (RF), and extreme learning machine (ELM) were adopted for predicting the yields of maize. All VIs calculated for each image captured during important phenological stages of maize were set as independent variables and the corresponding yields of each plot were defined as dependent variables. The ML models used the leave one out method (LOO), where the root mean square errors (RMSEs) were 2.157, 1.099, 1.146, and 1.698 (g/hundred grain weight) for BP, SVM, RF, and ELM. The mean absolute errors (MAEs) were 1.739, 0.886, 0.925, and 1.356 (g/hundred grain weight) for BP, SVM, RF, and ELM, respectively. Thus, the SVM method performed better in predicting the yields of maize than the other ML methods. Therefore, it is strongly suggested that the MRBVI calculated from images acquired at different growth stages integrated with advanced ML methods should be used for agricultural- and ecological-related chlorophyll estimation and yield predictions.