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Objective: To assess the intake of trans fatty acids (TFA) and other fatty acids in 14 Western European countries.Design and Subjects: A maximum of 100 foods per country were sampled and centrally analysed. Each country calculated the intake of individual trans and other fatty acids, clusters of fatty acids and total fat in adults and/or the total population using the best available national food consumption data set.Results: A wide variation was observed in the intake of total fat and (clusters) of fatty acids in absolute amounts. The variation in proportion of energy derived from total fat and from clusters of fatty acids was less. Only in Finland, Italy, Norway and Portugal total fat did provide on average less than 35% of energy intake. Saturated fatty acids (SFA) provided on average between 10% and 19% of total energy intake, with the lowest contribution in most Mediterranean countries. TFA intake ranged from 0.5% (Greece, Italy) to 2.1% (Iceland) of energy intake among men and from 0.8% (Greece) to 1.9% among women (Iceland) (1.2-6.7 g/d and 1.7-4.1 g/d, respectively). The TFA intake was lowest in Mediterranean countries (0.5-0.8 en%) but was also below 1% of energy in Finland and Germany. Moderate intakes were seen in Belgium, The Netherlands, Norway and UK and highest intake in Iceland. Trans isomers of C18:1 were the most TFA in the diet. Monounsaturated fatty acids contributed 9-12% of mean daily energy intake (except for Greece, nearly 18%) and polyunsaturated fatty acids 3-7%.Conclusion: The current intake of TFA in most Western European countries does not appear to be a reason for major concern. In several countries a considerable proportion of energy was derived from SFA. It would therefore be prudent to reduce intake of all cholesterol-raising fatty acids, TFA included. [ABSTRACT FROM AUTHOR]

This paper presents a simple algorithm for verifying the non-singularity of parametric transformations with quadratic Jacobian determinants. The method is suitable for such transformations applied to all convex polygonal two-dimensional master-elements, but emphasis is placed on the triangle and the square. Geometric insight is used to curtail testing procedures where possible. The algorithm is compared for efficiency to a related procedure in which no use is made of the geometry of the implied curves. Results indicate that the geometric procedure, while slower in some cases owing to additional tests, is considerably more efficient for those cases where the geometry allows early termination of the algorithm. [ABSTRACT FROM AUTHOR]

Background: Evidence on the relation between trans fatty acid intake and coronary heart disease is limited. We investigated this relation in a Dutch population with a fairly high trans fatty acid intake, including trans fatty acids from partly hydrogenated fish oils.Methods: We prospectively studied 667 men of the Zutphen Elderly Study aged 64-84 years and free of coronary heart disease at baseline. We used dietary surveys to establish the participants' food consumption patterns. Information on risk factors and diet was obtained in 1985, 1990, and 1995. After 10 years of follow-up from 1985-95, there were 98 cases of fatal or non-fatal coronary heart disease.Findings: Between 1985 and 1995, average trans fatty acid intake decreased from 4.3% to 1.9% of energy. After adjustment for age, body mass index, smoking, and dietary covariates, trans fatty acid intake at baseline was positively associated with the 10-year risk of coronary heart disease. The relative risk for a difference of 2% of energy in trans fatty acid intake at baseline was 1.28 (95% CI 1.01-1.61).Interpretation: A high intake of trans fatty acids (all types of isomers) contributes to the risk of coronary heart disease. The substantial decrease in trans fatty acid intake, mainly due to industrial lowering of trans contents in Dutch edible fats, could therefore have had a large public-health impact. [ABSTRACT FROM AUTHOR]

Objective: To systematically describe the next relevant aspects of tendotonometry in (1) its validity and reliability, (2) differences between populations, (3) the effect of interventions, and (4) differences between healthy and symptomatic Achilles tendon (AT) and patellar tendon (PT)., Data Sources: Three online databases (PubMed, Embase, and EBSCOhost) were systematically searched on the 10th of October 2023. All scientific literature concerning the use of tendotonometry in assessing tendon stiffness was collected. Articles were eligible if tendotonometry with a myotonometer digital palpation device was used to assess PT or AT stiffness in adults., Main Results: Thirty-four studies were included, which were categorized into studies regarding the (1a) reliability and (1b) validity of tendotonometry, (2) differences in stiffness between populations, (3) changes in stiffness due to interventions, (4) stiffness of healthy compared with injured tendons, and (5) other observational studies. The inter-rater and intrarater reliability of tendotonometry appeared to be good in assessing AT and PT stiffness, with only moderate evidence for the AT and inconclusive evidence for the PT. There is high certainty evidence that tendotonometry can detect differences in AT and PT stiffness after training interventions. Inconsistent results were found for the adequacy of tendotonometry to detect differences in AT and PT stiffness between populations., Conclusions: This review shows a potential role for tendotonometry in measuring tendon stiffness. However, more research is needed for validating the use of tendotonometry in AT and PT and its exact clinical interpretation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Auditory speech can be difficult to understand but seeing the articulatory movements of a speaker can drastically improve spoken-word recognition and, on the longer-term, it helps listeners to adapt to acoustically distorted speech. Given that individuals with developmental dyslexia (DD) have sometimes been reported to rely less on lip-read speech than typical readers, we examined lip-read-driven adaptation to distorted speech in a group of adults with DD ( N = 29) and a comparison group of typical readers ( N = 29). Participants were presented with acoustically distorted Dutch words (six-channel noise-vocoded speech, NVS) in audiovisual training blocks (where the speaker could be seen) interspersed with audio-only test blocks. Results showed that words were more accurately recognized if the speaker could be seen (a lip-read advantage), and that performance steadily improved across subsequent auditory-only test blocks (adaptation). There were no group differences, suggesting that perceptual adaptation to disrupted spoken words is comparable for dyslexic and typical readers. These data open up a research avenue to investigate the degree to which lip-read-driven speech adaptation generalizes across different types of auditory degradation, and across dyslexic readers with decoding versus comprehension difficulties.

Our percept of the world is not solely determined by what we perceive and process at a given moment in time, but also depends on what we processed recently. In the present study, we investigate whether the perceived emotion of a spoken sentence is contingent upon the emotion of an auditory stimulus on the preceding trial (i.e., serial dependence). Thereto, participants were exposed to spoken sentences that varied in emotional affect by changing the prosody that ranged from 'happy' to 'fearful'. Participants were instructed to rate the emotion. We found a positive serial dependence for emotion processing whereby the perceived emotion was biased towards the emotion on the preceding trial. When we introduced 'no-go' trials (i.e., no rating was required), we found a negative serial dependence when participants knew in advance to withhold their response on a given trial (Experiment 2) and a positive serial dependence when participants received the information to withhold their response after the stimulus presentation (Experiment 3). We therefore established a robust serial dependence for emotion processing in speech and introduce a methodology to disentangle perceptual from post-perceptual processes. This approach can be applied to the vast majority of studies investigating sequential dependencies to separate positive from negative serial dependence., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Trust is an aspect critical to human social interaction and research has identified many cues that help in the assimilation of this social trait. Two of these cues are the pitch of the voice and the width-to-height ratio of the face (fWHR). Additionally, research has indicated that the content of a spoken sentence itself has an effect on trustworthiness; a finding that has not yet been brought into multisensory research. The current research aims to investigate previously developed theories on trust in relation to vocal pitch, fWHR, and sentence content in a multimodal setting. Twenty-six female participants were asked to judge the trustworthiness of a voice speaking a neutral or romantic sentence while seeing a face. The average pitch of the voice and the fWHR were varied systematically. Results indicate that the content of the spoken message was an important predictor of trustworthiness extending into multimodality. Further, the mean pitch of the voice and fWHR of the face appeared to be useful indicators in a multimodal setting. These effects interacted with one another across modalities. The data demonstrate that trust in the voice is shaped by task-irrelevant visual stimuli. Future research is encouraged to clarify whether these findings remain consistent across genders, age groups, and languages.

Humans' extraordinary ability to understand speech in noise relies on multiple processes that develop with age. Using magnetoencephalography (MEG), we characterize the underlying neuromaturational basis by quantifying how cortical oscillations in 144 participants (aged 5-27 years) track phrasal and syllabic structures in connected speech mixed with different types of noise. While the extraction of prosodic cues from clear speech was stable during development, its maintenance in a multi-talker background matured rapidly up to age 9 and was associated with speech comprehension. Furthermore, while the extraction of subtler information provided by syllables matured at age 9, its maintenance in noisy backgrounds progressively matured until adulthood. Altogether, these results highlight distinct behaviorally relevant maturational trajectories for the neuronal signatures of speech perception. In accordance with grain-size proposals, neuromaturational milestones are reached increasingly late for linguistic units of decreasing size, with further delays incurred by noise., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

When listening to distorted speech, does one become a better listener by looking at the face of the speaker or by reading subtitles that are presented along with the speech signal? We examined this question in two experiments in which we presented participants with spectrally distorted speech (4-channel noise-vocoded speech). During short training sessions, listeners received auditorily distorted words or pseudowords that were partially disambiguated by concurrently presented lipread information or text. After each training session, listeners were tested with new degraded auditory words. Learning effects (based on proportions of correctly identified words) were stronger if listeners had trained with words rather than with pseudowords (a lexical boost), and adding lipread information during training was more effective than adding text (a lipread boost). Moreover, the advantage of lipread speech over text training was also found when participants were tested more than a month later. The current results thus suggest that lipread speech may have surprisingly long-lasting effects on adaptation to distorted speech., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Pourhashemi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We investigated how aging modulates lexico-semantic processes in the visual (seeing written items), auditory (hearing spoken items) and audiovisual (seeing written items while hearing congruent spoken items) modalities. Participants were young and older adults who performed a delayed lexical decision task (LDT) presented in blocks of visual, auditory, and audiovisual stimuli. Event-related potentials (ERPs) revealed differences between young and older adults despite older adults' ability to identify words and pseudowords as accurately as young adults. The observed differences included more focalized lexico-semantic access in the N400 time window in older relative to young adults, stronger re-instantiation and/or more widespread activity of the lexicality effect at the time of responding, and stronger multimodal integration for older relative to young adults. Our results offer new insights into how functional neural differences in older adults can result in efficient access to lexico-semantic representations across the lifespan., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Spoken language comprehension is a fundamental component of our cognitive skills. We are quite proficient at deciphering words from the auditory input despite the fact that the speech we hear is often masked by noise such as background babble originating from talkers other than the one we are attending to. To perceive spoken language as intended, we rely on prior linguistic knowledge and context. Prior knowledge includes all sounds and words that are familiar to a listener and depends on linguistic experience. For bilinguals, the phonetic and lexical repertoire encompasses two languages, and the degree of overlap between word forms across languages affects the degree to which they influence one another during auditory word recognition. To support spoken word recognition, listeners often rely on semantic information (i.e., the words we hear are usually related in a meaningful way). Although the number of multilinguals across the globe is increasing, little is known about how crosslinguistic effects (i.e., word overlap) interact with semantic context and affect the flexible neural systems that support accurate word recognition. The current multi-echo functional magnetic resonance imaging (fMRI) study addresses this question by examining how prime-target word pair semantic relationships interact with the target word's form similarity (cognate status) to the translation equivalent in the dominant language (L1) during accurate word recognition of a non-dominant (L2) language. We tested 26 early-proficient Spanish-Basque (L1-L2) bilinguals. When L2 targets matching L1 translation-equivalent phonological word forms were preceded by unrelated semantic contexts that drive lexical competition, a flexible language control (fronto-parietal-subcortical) network was upregulated, whereas when they were preceded by related semantic contexts that reduce lexical competition, it was downregulated. We conclude that an interplay between semantic and crosslinguistic effects regulates flexible control mechanisms of speech processing to facilitate L2 word recognition, in noise., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2021. Published by Elsevier Inc.)

Background: One potentially relevant neurophysiological marker of internalizing problems (anxiety/depressive symptoms) is the late positive potential (LPP), as it is related to processing of emotional stimuli. For the first time, to our knowledge, we investigated the value of the LPP as a neurophysiological marker for internalizing problems and specific anxiety and depressive symptoms, at preschool age., Method: At age 4 years, children (N = 84) passively viewed a series of neutral, pleasant, and unpleasant pictures selected from the International Affective Pictures System. Affective picture processing was measured via the LPP (EEG recorded) and mothers reported on child behavior via the Child Behavior Checklist 1 ½ - 5 (internalizing, DSM-anxiety, DSM-affective/depression subscales). Difference scores between the neutral and affective pictures (i.e., neutral-pleasant and neutral-unpleasant) were computed for posterior, central and anterior brain locations for early (300-700 ms), middle (700-1200 ms) and late (1200-2000 ms) time windows., Results: Greater LPP difference scores for pleasant images in the anterior recording site, in the middle time window, were associated with greater internalizing behaviors. Greater DSM-anxiety symptoms were associated with greater LPP difference scores for unpleasant and pleasant images. After correcting for multiple testing, only the association between greater DSM-affective/depression symptoms and greater LPP difference scores for unpleasant images in the anterior recording site (early time window) remained significant., Discussion: Our study has identified a potential neural marker of preschool internalizing problems. Children with larger LPPs to unpleasant images may be at greater risk of internalizing problems, potentially due to an increased emotional reactivity., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Humans quickly adapt to variations in the speech signal. Adaptation may surface as recalibration , a learning effect driven by error-minimisation between a visual face and an ambiguous auditory speech signal, or as selective adaptation , a contrastive aftereffect driven by the acoustic clarity of the sound. Here, we examined whether these aftereffects occur for vowel identity and voice gender. Participants were exposed to male, female, or androgynous tokens of speakers pronouncing /e/, /ø/, (embedded in words with a consonant-vowel-consonant structure), or an ambiguous vowel halfway between /e/ and /ø/ dubbed onto the video of a male or female speaker pronouncing /e/ or /ø/. For both voice gender and vowel identity, we found assimilative aftereffects after exposure to auditory ambiguous adapter sounds, and contrastive aftereffects after exposure to auditory clear adapter sounds. This demonstrates that similar principles for adaptation in these dimensions are at play.

In two experiments, we investigated the relationship between lexical access processes, and processes that are specifically related to making lexical decisions. In Experiment 1, participants performed a standard lexical decision task in which they had to respond as quickly and as accurately as possible to visual (written), auditory (spoken) and audiovisual (written + spoken) items. In Experiment 2, a different group of participants performed the same task but were required to make responses after a delay. Linear mixed effect models on reaction times and single trial Event-Related Potentials (ERPs) revealed that ERP lexicality effects started earlier in the visual than auditory modality, and that effects were driven by the written input in the audiovisual modality. More negative ERP amplitudes predicted slower reaction times in all modalities in both experiments. However, these predictive amplitudes were mainly observed within the window of the lexicality effect in Experiment 1 (the speeded task), and shifted to post-response-probe time windows in Experiment 2 (the delayed task). The lexicality effects lasted longer in Experiment 1 than in Experiment 2, and in the delayed task, we additionally observed a "re-instantiation" of the lexicality effect related to the delayed response. Delaying the response in an otherwise identical lexical decision task thus allowed us to separate lexical access processes from processes specific to lexical decision., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lip-reading is crucial for understanding speech in challenging conditions. But how the brain extracts meaning from, silent, visual speech is still under debate. Lip-reading in silence activates the auditory cortices, but it is not known whether such activation reflects immediate synthesis of the corresponding auditory stimulus or imagery of unrelated sounds. To disentangle these possibilities, we used magnetoencephalography to evaluate how cortical activity in 28 healthy adult humans (17 females) entrained to the auditory speech envelope and lip movements (mouth opening) when listening to a spoken story without visual input (audio-only), and when seeing a silent video of a speaker articulating another story (video-only). In video-only, auditory cortical activity entrained to the absent auditory signal at frequencies <1 Hz more than to the seen lip movements. This entrainment process was characterized by an auditory-speech-to-brain delay of ∼70 ms in the left hemisphere, compared with ∼20 ms in audio-only. Entrainment to mouth opening was found in the right angular gyrus at <1 Hz, and in early visual cortices at 1-8 Hz. These findings demonstrate that the brain can use a silent lip-read signal to synthesize a coarse-grained auditory speech representation in early auditory cortices. Our data indicate the following underlying oscillatory mechanism: seeing lip movements first modulates neuronal activity in early visual cortices at frequencies that match articulatory lip movements; the right angular gyrus then extracts slower features of lip movements, mapping them onto the corresponding speech sound features; this information is fed to auditory cortices, most likely facilitating speech parsing. SIGNIFICANCE STATEMENT Lip-reading consists in decoding speech based on visual information derived from observation of a speaker's articulatory facial gestures. Lip-reading is known to improve auditory speech understanding, especially when speech is degraded. Interestingly, lip-reading in silence still activates the auditory cortices, even when participants do not know what the absent auditory signal should be. However, it was uncertain what such activation reflected. Here, using magnetoencephalographic recordings, we demonstrate that it reflects fast synthesis of the auditory stimulus rather than mental imagery of unrelated, speech or non-speech, sounds. Our results also shed light on the oscillatory dynamics underlying lip-reading., (Copyright © 2020 the authors.)

Speech perception is influenced by vision through a process of audiovisual integration. This is demonstrated by the McGurk illusion where visual speech (for example /ga/) dubbed with incongruent auditory speech (such as /ba/) leads to a modified auditory percept (/da/). Recent studies have indicated that perception of the incongruent speech stimuli used in McGurk paradigms involves mechanisms of both general and audiovisual speech specific mismatch processing and that general mismatch processing modulates induced theta-band (4-8 Hz) oscillations. Here, we investigated whether the theta modulation merely reflects mismatch processing or, alternatively, audiovisual integration of speech. We used electroencephalographic recordings from two previously published studies using audiovisual sine-wave speech (SWS), a spectrally degraded speech signal sounding nonsensical to naïve perceivers but perceived as speech by informed subjects. Earlier studies have shown that informed, but not naïve subjects integrate SWS phonetically with visual speech. In an N1/P2 event-related potential paradigm, we found a significant difference in theta-band activity between informed and naïve perceivers of audiovisual speech, suggesting that audiovisual integration modulates induced theta-band oscillations. In a McGurk mismatch negativity paradigm (MMN) where infrequent McGurk stimuli were embedded in a sequence of frequent audio-visually congruent stimuli we found no difference between congruent and McGurk stimuli. The infrequent stimuli in this paradigm are violating both the general prediction of stimulus content, and that of audiovisual congruence. Hence, we found no support for the hypothesis that audiovisual mismatch modulates induced theta-band oscillations. We also did not find any effects of audiovisual integration in the MMN paradigm, possibly due to the experimental design., Competing Interests: The authors have declared that no competing interests exist.

Although the default state of the world is that we see and hear other people talking, there is evidence that seeing and hearing ourselves rather than someone else may lead to visual (i.e., lip-read) or auditory "self" advantages. We assessed whether there is a "self" advantage for phonetic recalibration (a lip-read driven cross-modal learning effect) and selective adaptation (a contrastive effect in the opposite direction of recalibration). We observed both aftereffects as well as an on-line effect of lip-read information on auditory perception (i.e., immediate capture ), but there was no evidence for a "self" advantage in any of the tasks (as additionally supported by Bayesian statistics). These findings strengthen the emerging notion that recalibration reflects a general learning mechanism, and bolster the argument that adaptation depends on rather low-level auditory/acoustic features of the speech signal.

Hyperscanning refers to obtaining simultaneous neural recordings from more than one person (Montage et al., 2002 [1]), that can be used to study interactive situations. In particular, hyperscanning with Electroencephalography (EEG) is becoming increasingly popular since it allows researchers to explore the interactive brain with a high temporal resolution. Notably, there is a 40-year gap between the first instance that simultaneous measurement of EEG activity was mentioned in the literature (Duane and Behrendt, 1965 [2]), and the first actual description of an EEG hyperscanning setup being implemented (Babiloni et al., 2006 [3]). To date, specific EEG hyperscanning devices have not yet been developed and EEG hyperscanning setups are not usually described with sufficient detail to be easily reproduced. Here, we offer a step-by-step description of solutions to many of these technological challenges. Specifically, we describe and provide customized implementations of EEG hyperscanning setups using hardware and software from different companies: Brain Products, ANT, EGI, and BioSemi. •Necessary details to set up a functioning EEG hyperscanning protocol are provided.•The setups allow independent measures and measures of synchronization between the signals of two different brains.•Individual electrical Ground and Reference is obtained in all discussed systems.

Perception of vocal affect is influenced by the concurrent sight of an emotional face. We demonstrate that the sight of an emotional face also can induce recalibration of vocal affect. Participants were exposed to videos of a 'happy' or 'fearful' face in combination with a slightly incongruous sentence with ambiguous prosody. After this exposure, ambiguous test sentences were rated as more 'happy' when the exposure phase contained 'happy' instead of 'fearful' faces. This auditory shift likely reflects recalibration that is induced by error minimization of the inter-sensory discrepancy. In line with this view, when the prosody of the exposure sentence was non-ambiguous and congruent with the face (without audiovisual discrepancy), aftereffects went in the opposite direction, likely reflecting adaptation. Our results demonstrate, for the first time, that perception of vocal affect is flexible and can be recalibrated by slightly discrepant visual information.

Incongruent audiovisual speech stimuli can lead to perceptual illusions such as fusions or combinations. Here, we investigated the underlying audiovisual integration process by measuring ERPs. We observed that visual speech-induced suppression of P2 amplitude (which is generally taken as a measure of audiovisual integration) for fusions was similar to suppression obtained with fully congruent stimuli, whereas P2 suppression for combinations was larger. We argue that these effects arise because the phonetic incongruency is solved differently for both types of stimuli., (© 2017 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Perceiving linguistic input is vital for human functioning, but the process is complicated by the fact that the incoming signal is often degraded. However, humans can compensate for unimodal noise by relying on simultaneous sensory input from another modality. Here, we investigated noise-compensation for spoken and printed words in two experiments. In the first behavioral experiment, we observed that accuracy was modulated by reaction time, bias and sensitivity, but noise compensation could nevertheless be explained via accuracy differences when controlling for RT, bias and sensitivity. In the second experiment, we also measured Event Related Potentials (ERPs) and observed robust electrophysiological correlates of noise compensation starting at around 350 ms after stimulus onset, indicating that noise compensation is most prominent at lexical/semantic processing levels., Competing Interests: The authors declare no competing financial interests.

Lip-read speech suppresses and speeds up the auditory N1 and P2 peaks, but these effects are not always observed or reported. Here, the robustness of lip-read-induced N1/P2 suppression and facilitation in phonetically congruent audiovisual speech was assessed by analyzing peak values that were taken from published plots and individual data. To determine whether adhering to the additive model of AV integration (i.e., A+V ≠ AV, or AV-V ≠ A) is critical for correct characterization of lip-read-induced effects on the N1 and P2, auditory data was compared to AV and to AV-V. On average, the N1 and P2 were consistently suppressed and sped up by lip-read information, with no indication that AV integration effects were significantly modulated by whether or not V was subtracted from AV. To assess the possibility that variability in observed N1/P2 amplitudes and latencies may explain why N1/P2 suppression and facilitation are not always found, additional correlations between peak values and size of the AV integration effects were computed. These analyses showed that N1/P2 peak values correlated with the size of AV integration effects. However, it also became apparent that a portion of the AV integration effects was characterized by lip-read-induced peak enhancements and delays rather than suppressions and facilitations, which, for the individual data, seemed related to particularly small/early A-only peaks and large/late AV(-V) peaks., (© 2016 Society for Psychophysiological Research.)

Background: It remains important to develop the next generation of influenza vaccines that can provide protection against vaccine mismatched strains and to be prepared for potential pandemic outbreaks. To achieve this, the understanding of the immunological parameters that mediate such broad protection is crucial., Method: In the current study we assessed the contribution of humoral and cellular immune responses to heterosubtypic protection against H5N1 induced by a Matrix-M (MM) adjuvanted seasonal influenza vaccine by serum transfer and T-cell depletion studies., Results: We demonstrate that the heterosubtypic protection against H5N1 induced by MM adjuvanted vaccine is partially mediated by antibodies. The serum contained both H5N1 cross-reactive hemagglutinin (HA)- and neuraminidase (NA)-specific antibodies but with limited virus neutralizing and no hemagglutination inhibiting activity. The cross-reactive antibodies induced antibody-dependent cellular cytotoxicity (ADCC) in vitro, suggesting a role for the Fc part of the antibodies in protection against H5N1. Besides H5N1 specific antibody responses, cross-reactive HA- and NA-specific T-cell responses were induced by the adjuvanted vaccine. T-cell depletion experiments demonstrated that both CD4+ and CD8+ T cells contribute to protection., Conclusion: Our study demonstrates that cross-protection against H5N1 induced by MM adjuvanted seasonal virosomal influenza vaccine requires both the humoral and cellular arm of the immune system.

Background: Influenza virus infections are responsible for significant morbidity worldwide and therefore it remains a high priority to develop more broadly protective vaccines. Adjuvation of current seasonal influenza vaccines has the potential to achieve this goal., Methods: To assess the immune potentiating properties of Matrix-M™, mice were immunized with virosomal trivalent seasonal vaccine adjuvated with Matrix-M™. Serum samples were isolated to determine the hemagglutination inhibiting (HAI) antibody titers against vaccine homologous and heterologous strains. Furthermore, we assess whether adjuvation with Matrix-M™ broadens the protective efficacy of the virosomal trivalent seasonal vaccine against vaccine homologous and heterologous influenza viruses., Results: Matrix-M™ adjuvation enhanced HAI antibody titers and protection against vaccine homologous strains. Interestingly, Matrix-M™ adjuvation also resulted in HAI antibody titers against heterologous influenza B strains, but not against the tested influenza A strains. Even though the protection against heterologous influenza A was induced by the adjuvated vaccine, in the absence of HAI titers the protection was accompanied by severe clinical scores and body weight loss. In contrast, in the presence of heterologous HAI titers full protection against the heterologous influenza B strain without any disease symptoms was obtained., Conclusion: The results of this study emphasize the promising potential of a Matrix-M™-adjuvated seasonal trivalent virosomal influenza vaccine. Adjuvation of trivalent virosomal vaccine does not only enhance homologous protection, but in addition induces protection against heterologous strains and thus provides overall more potent and broad protective immunity.

There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV) adjuvated with the saponin-based adjuvant Matrix-M (MM) can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8(+) T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines., (Copyright © 2015, Wegmann et al.)