Anacardic acid (AA) is a bioactive phytochemical found in the nutshell of Anacardium occidentale, a tropical plant originally from Brazil. In this work, cross-linked anacardic acid nanocapsules (NC) were obtained by interfacial polymerization carried out using the inverse miniemulsion technique with 2,4-toluene diisocyanate (TDI). For this purpose, a functionalized monomer from AA was synthesized for formation of lipase-cleavable ester linkages by coupling of amino acids. The synthesis was planned so that when these ester linkages get exposed to an enzyme, they are broken down and released AA. Furthermore, the N-termini of the coupled amino compounds were used as sites for the polyaddition with TDI at the droplet interface in the inverse miniemulsion. The permeability of the shell was studied on the fluorescent dye, sulforhodamine 101 (SR101), using fuorescence spectroscopy After redispersion in water, the enzymatic cleavage of NC and the release of the SR101 were both monitored in real time. The released AA was proven to be active in vitro against Bacillus subtilis colonies in the bacterial tests. The results indicate that the use of NC is a promising strategy, which can make feasible the application of AA for therapeutic purposes and as nanocarriers for the delivery of active components.

Abstract Objective: To identify and describe learnings from past pandemics and to suggest a framework for vaccine development as part of epi/pandemic readiness. Source of data: Articles/ reviews/letters on pandemic preparedness/ vaccines published between 2005 and 2022 in PubMed, MEDLINE, MedRxiv, BioRxiv, Research Square, Gates Open Research; who. int, cepi.net, visualcapitalist.com, airfinity.com, ted.com websites; press releases. Summary of findings: Disease pandemics caused by emerging pathogens impacted the social development, health and wealth of most societies in human history. In an outbreak, the first months determine its course. To block an exponential spread and the development of an epi/ pandemic early, vaccine availability in sufficient quantities is of paramount importance. It is inevitable that new human viruses will emerge. Any future pandemic will come likely from RNA viruses through zoonotic or vector transmission, but we cannot predict when or where “Disease X” will strike. Public health, scientific and societal readiness plans need to include: continuous identification of new viruses in common mammalian reservoir hosts; continuous epidemiological surveillance, including wastewater sampling; establishment of prototype vaccine libraries against various virus families sharing functional and structural properties; testing of various and innovative vaccine platforms including mRNA, vector, nasal or oral vaccines for suitability by virus family; functional clinical trial sites and laboratory networks in various geographies; more efficient phasing of preclinical and clinical activities; global harmonization and streamlining of regulatory requirements including pre-established protocols; and societal preparedness including combating any pandemic of misinformation. Conclusions: “Outbreaks are unavoidable, pandemics are optional”.

Abstract Objective: Through a literature review, make recommendations regarding immunizations in people living with Inborn Error of Metabolism (IEM) in Brazil, assess the possible impact on metabolic decompensations after immunization, and if this specific population may have an impaired immune response to vaccines. Source of data: The MeSH Terms vaccination OR vaccine OR immunization associated with the term inborn error of metabolism AND recommendation were used in combination with search databases. Only articles published after 1990, in the languages English, Spanish, French or Portuguese, human-related were included. Synthesis of data: A total of 44 articles were included to make the following recommendations. Individuals with IEMs need to be up to date with their immunizations. Regarding which vaccines should be offered, children and adults should follow the routine immunization schedules locally available, including the COVID-19 vaccines. The only exception is the rotavirus vaccine for hereditary fructose intolerance. The benefit of immunization outweighs the very low risk of metabolic decompensation. Since not all patients will have an adequate immune response, measuring antibody conversion and titers is recommended Conclusions: All patients should receive age-appropriate immunizations in their respective schedules without delays. The only situation when vaccination may be contraindicated is with oral rotavirus vaccine in hereditary fructose intolerance. Monitoring the levels of antibodies should be done to detect any immune dysfunction or the necessity for boosters. A personalized immunization schedule is ideal for patients with IEMs. The reference organizations could improve their recommendations to address all IEMs, not only some of them.

OBJECTIVE: To evaluate a killed oral cholera vaccine produced in Viet Nam, and to compare the Vietnamese vaccine with one that is licensed internationally. METHOD: Two-dose regimens of a locally produced, bivalent, anti-O1, anti-O139 killed oral whole-cell cholera vaccine (biv-WC) and of a commercially available, monovalent (anti-O1) oral recombinant B subunit-killed whole-cell cholera vaccine (rBS-WC) were compared in two trials in Viet Nam. In the first trial, 144 adults were randomized to biv-WC with or without buffer, rBS-WC with buffer, or placebo without buffer. In the second, 103 children aged 1-12 years were randomized to biv-WC without buffer, rBS-WC with buffer, or placebo without buffer. FINDINGS: No regimen was associated with significant side-effects. In adults, ca 60% of recipients of either vaccine exhibited at least fourfold serum anti-O1 vibriocidal antibody responses and ca 40% of recipients of biv-WC demonstrated anti-O139 vibriocidal responses. Both anti-O1 (ca 90% in each vaccine groupand anti-O139 (68% in the biv-WC group) vibriocidal responses occurred more frequently in children. The responses to biv-WC were unaffected by the receipt of buffer. CONCLUSION: It was concluded that biv-WC was safe and immunogenic, that it could be administered without buffer, and that it could elicit robust immune responses even in children, for whom the risk of endemic cholera is highest.

OBJETIVO: Comparar una vacuna anticolérica producida a nivel local con otra vacuna comercial. MÉTODOS: Mediante dos ensayos llevados a cabo en Viet Nam, se procedió a comparar los efectos de regímenes de dos dosis de una vacuna (local) anticolérica oral inactivada de células enteras de tipo bivalente contra las cepas O1 y O139 (biv-WC) con los de otra vacuna (comercial) anticolérica oral inactivada de células enteras de tipo monovalente basada en la subunidad B recombinante (anti-O1) (rBS-WC). En el primer ensayo se distribuyó aleatoriamente a 144 adultos para que recibieran ya fuese biv-WC con o sin tampón, rBS-WC con tampón, o placebo sin tampón. En el segundo se designó aleatoriamente a 103 niños de 1 a 12 años para que recibieran ya fuera biv-WC sin tampón, rBS-WC con tampón o placebo sin tampón. RESULTADOS: Ninguno de los regímenes tuvo efectos secundarios importantes. En los adultos, aproximadamente un 60% de los receptores de cualquiera de las vacunas mostró como mínimo una cuadruplicación de la producción de anticuerpos vibriocidas anti-O1 en el suero, y un 40% de los receptores de la biv-WC mostró respuestas vibriocidas anti-O139. Las respuestas a la biv-WC no se vieron afectadas por la recepción de tampón. Las respuestas vibriocidas, tanto anti-O1 (un 90% en cada grupo) como anti-O139 (68% en el grupo tratado con biv-WC), fueron más frecuentes en los niños que en los adultos. CONCLUSIÓN: La vacuna biv-WC es segura e inmunogénica, se puede administrar sin tampón, y puede inducir respuestas inmunitarias robustas incluso en los niños, que presentan un mayor riesgo de cólera endémico.

OBJECTIF: Comparer un vaccin anticholérique de production locale avec un vaccin disponible dans le commerce. MÉTHODES: Lors de deux essais réalisés au Viet Nam, on a comparé un schéma en deux doses d'un vaccin anticholérique oral tué à germes entiers, bivalent anti-O1, anti-O139 de production locale (biv-WC) et d'un vaccin anticholérique oral contenant la sous-unité B recombinante et des germes entiers tués, monovalent anti-O1, disponible dans le commerce (rBS-WC). Dans le premier essai, 144 adultes ont reçu après tirage au sort le vaccin biv-WC avec ou sans tampon, le vaccin rBS-WC avec tampon, ou un placebo sans tampon. Dans le deuxième essai, 103 enfants de 1 à 12 ans ont reçu après tirage au sort le vaccin biv-WC sans tampon, le vaccin rBS-WC avec tampon, ou un placebo sans tampon. RÉSULTATS: Aucun schéma n'a été associé à des effets secondaires significatifs. Chez les adultes, environ 60 % des sujets vaccinés par l'un ou l'autre produit ont présenté au moins un quadruplement des anticorps vibriocides anti-O1 et environ 40 % des sujets ayant reçu le vaccin biv-WC ont présenté une réponse vibriocide anti- O139. La réponse au vaccin biv-WC n'était pas modifiée par la présence d'un tampon. Les réponses en anticorps vibriocides anti-O1 (environ 90 % dans chaque groupe) et anti-O139 (68 % dans le groupe biv-WC) étaient observées plus fréquemment chez les enfants que chez les adultes. CONCLUSION: Il a été conclu que le vaccin biv-WC était efficace et sans danger, qu'il pouvait être administré sans tampon et qu'il pouvait induire une forte réponse immunitaire même chez les enfants pour lesquels le risque de choléra endémique est le plus élevé.

In 1995, the WHO Global Programme for Vaccines and Immunization established a vaccine trial registry. As of September 1996, this registry included 50 WHO supported vaccine trials, of which 25 (50%) were completed studies. The vaccines most frequently tested have been against measles (9 trials), poliovirus (8 trials), cholera (8 trials), enterotoxigenic Escherichia coli (4 trials), and pneumococcus (4 trials). Nearly 80% of these trials have been conducted in developing countries, with the largest number being in Africa. Among the 25 completed trials, outcomes measured were immune response (24 trials), adverse reactions (13 trials), morbidity (4 trials), and mortality (1 trial). WHO's contributions to these studies include direct funding, assistance with study design, site visits, data analysis, vaccine procurement, and vaccine potency testing.

En 1995, el Programa Mundial de Vacunas e Inmunización de la OMS estableció un registro para ensayos con vacunas. En septiembre de 1996, este registro contenía 50 ensayos de vacunación patrocinados por la OMS, de los cuales 25 (50%) eran estudios ya terminados. Las vacunas que se habían estudiado con mayor frecuencia fueron las de sarampión (9 ensayos), poliovirus (8 ensayos), cólera (8 ensayos), Escherichia coli enterotoxígena (4 ensayos) y neumococo (4 ensayos). Casi 80% de estos ensayos se llevaron a cabo en países en desarrollo, principalmente en el África. En los 25 ensayos ya terminados, los resultados investigados fueron la respuesta inmunitaria (24 ensayos), las reacciones adversas (13 ensayos), la morbilidad (4 ensayos) y la mortalidad (1 ensayo). La OMS contribuyó a estos ensayos con el aporte indirecto de fondos, ayuda con el diseño metodológico, visitas a las localidades, el análisis de los datos, la adquisición de vacunas y la investigación de su potencia.