Nutritional Quality of the Mid-Afternoon Snack of Schooled Children between the Ages of 3 and 12 Years in Three Areas in Spain.

BACKGROUND: The aim of this study was to analyze the nutritional quality of mid-afternoon snacks for schooled children aged 3 to 12 years in three areas of Catalonia (Spain). METHODS: A descriptive observational study collected information on habits and the mid-afternoon snack of 782 schooled children aged 3 to 12 years in three cities, Barcelona, Girona, and Lleida, located in Catalonia (Spain). The children's families voluntarily agreed to complete an online questionnaire that collected information about demographic data and snacking habits in the afternoon, as well as a record of mid-afternoon snack intake over three school days. RESULTS: A total of 2163 mid-afternoon snacks were analyzed from a sample of 764 families with 3 to 12 year-old children. Sandwiches emerged as the most prevalent choice, accounting for 41.89%, followed by pastries at 23.86%, fruit at 14.38%, and a combination of fruit and pastries at 6.29%. Of the mid-afternoon snacks recorded, 22.19% were healthy, 20.90% were quite healthy, 12.85% were quite unhealthy, and 44.06% were unhealthy. CONCLUSIONS: The nutritional quality of mid-afternoon snacks for a large majority of schooled children should be improved. It is essential to develop food education programs to improve the quality of this intake from early childhood and to consider it as an opportunity to adjust the daily dietary requirements of Spanish children.

Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine, in non-human primates

SARS-CoV-2 emerged in December 2019 and quickly spread worldwide, continuously striking with an unpredictable evolution. Despite the success in vaccine production and mass vaccination programmes, the situation is not still completely controlled, and therefore accessible second-generation vaccines are required to mitigate the pandemic. We previously developed an adjuvanted vaccine candidate coded PHH-1V, based on a heterodimer fusion protein comprising the RBD domain of two SARS-CoV-2 variants. Here, we report data on the efficacy, safety, and immunogenicity of PHH-1V in cynomolgus macaques. PHH-1V prime-boost vaccination induces high levels of RBD-specific IgG and IgA binding and neutralising antibodies against several SARS-CoV-2 variants of concern, as well as a balanced Th1/Th2 cellular immune response. Remarkably, PHH-1V vaccination prevents SARS-CoV-2 replication in the lower respiratory tract and significantly reduces viral load in the upper respiratory tract after an experimental infection. These results highlight the potential use of the PHH-1V vaccine in humans, currently undergoing Phase III clinical trials.

Safety and Immunogenicity of a Recombinant Protein RBD Fusion Heterodimer Vaccine against SARS-CoV-2: preliminary results of a phase 1-2a dose-escalating, randomized, double-blind clinical trial.

BackgroundWe report safety, tolerability, and immunogenicity of a recombinant protein RBD-fusion heterodimeric vaccine against SARS-CoV-2 (PHH-1V). MethodsA dose-escalation, phase 1-2a, randomized clinical trial was performed in Catalonia, Spain. Each cohort had one safety sentinel that received PHH-1V vaccine of the corresponding dose, and remaining participants were randomly assigned to receive PHH-1V formulations [10{micro}g (n=5), 20{micro}g (n=10), 40{micro}g (n=10)] or control BNT162b2 (n=5). Two intramuscular doses (0-21 days) were administered. Primary endpoint was solicited events 7 days after each vaccination and secondary-exploratory endpoints were humoral and cellular immunogenicity. Findings30 young healthy adults were enrolled, thirteen were female. Vaccines were safe, well tolerated. The most common solicited events for all groups were tenderness and pain at the site of injection. The proportion of subjects with at least one reported local and/or systemic solicited adverse events (AE) after first or second vaccine dose were lowest in PHH-1V (n=21, 84%) than control group (n=5, 100%). AE were mild to moderate, and no severe AE nor AE of special interest were reported. All participants had a >4-fold change at day 35 in total binding antibodies from baseline. Variants of concern (VOC) alpha, beta, delta and gamma were evaluated using a SARS-CoV-2 pseudovirus-based neutralization assay. All groups had a significant geometric mean fold rise (p<.0001) at day 35 against all studied VOC. Similar results were obtained when a full replicative virus neutralization assay was carried out. InterpretationPHH-1V was safe, well tolerated, and induced robust humoral responses. These data support further exploration of PHH-1V in larger studies. FundingHIPRA ClinicalTrials.gov IdentifierNCT05007509 Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed up until August 1, 2021, with the terms "SARS-CoV-2", "COVID-19" and "vaccine". We initially identified 12,952 results but when added the terms "clinical trial" and "variants" this number decreased to 50. Of these references twelve were clinical trials, and although several vaccines were under development, and the ones that were already approved for administration in the general population described the neutralization effect to the different circulating variants of concern, we could not find any reference to a vaccine developed using variants of concern instead of ancestral Wuhan strain. Added value of this studyTo the best of our knowledge, our study is the first clinical trial to assess the effect as a primary series of a recombinant protein receptor-binding domain fusion heterodimer PHH-1V vaccine against SARS-CoV-2 not including the ancestral strain in its composition. This vaccine contains RBD from B{middle dot}1{middle dot}351 (beta) and B{middle dot}1{middle dot}1{middle dot}7 (alpha) variants and is co-formulated with an oil-in-water adjuvant emulsion. In this first-in-human randomized clinical trial, two doses of the SARS-CoV-2 PHH-1V vaccine in a range of 10 to 40 {micro}g/dose were safe and well-tolerated and induced robust humoral immune responses to different circulating variants of concern, including alpha (B1{middle dot}1{middle dot}7), beta (B{middle dot}1{middle dot}351), delta (B{middle dot}1{middle dot}617{middle dot}2) and gamma (P{middle dot}1). Additionally, the PHH-1V 40{micro}g dose vaccine elicited moderated cellular immune responses, particularly to variants of concern alpha and delta. Implications of all the available evidenceThese findings indicate that the recombinant protein receptor-binding domain fusion heterodimer vaccine PHH-1V is safe and immunogenic. Phase 2b and Phase 3 clinical trials are ongoing to further investigate its safety and protective efficacy as heterologous booster.

Safety and immunogenicity of the protein-based PHH-IV compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.

Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine -either heterologous (PHH-1V group) or homologous (BNT162b2 group)- in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus [≥]65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections [≥]14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p<0.0001), 1.31 (p=0.0007) and 0.86 (p=0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p<0.0001), 0.65 (p<0.0001) and 0.56 (p=0.003) for the Beta variant; 1.01 (p=0.92), 0.88 (p=0.11) and 0.52 (p=0.0003) for the Delta variant; and 0.59 (p=<0.0001), 0.66 (p<0.0001) and 0.57 (p=0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-{gamma} on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p=0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and Delta SARS-CoV-2 variants, as well as the currently circulating Omicron BA.1. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.

Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine candidate based on a novel recombinant RBD fusion heterodimer of SARS-CoV-2.

The current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease and decrease in mortality rates. However, new variants of concern (VoCs) are continuously evolving, making the development of new accessible COVID-19 vaccines essential in order to mitigate the pandemic. Here we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine candidate (PHH-1V) consisting of an RBD fusion heterodimer containing the B.1.351 and B.1.1.7 SARS-CoV-2 VoCs and formulated with the SQBA adjuvant, an oil-in-water emulsion produced by HIPRA. BALB/c and K18-hACE2 mice were immunized with different recombinant RBD fusion heterodimer doses, following a two-dose prime-and-boost schedule. Vaccination induced a CD4+ and CD8+ T cell response and RBD-binding antibodies with neutralising activity against various VoCs with a good tolerability profile. Significantly, a 10-{micro}g or 20-{micro}g RBD fusion heterodimer/dose vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice. These findings demonstrate the feasibility of this recombinant vaccine strategy.