For neonates without maternal-immunity, mixed-vaccination schedules that include the aP-and OMVP-vaccines appear to be the most appropriate to induce protection in the pups. For offspring from immune mothers, to avoid blunting-effect, NI should be carried out with vaccines other than those applied during pregnancy.

Pertussis resurgence had been attributed to waning vaccine immunity and Bordetella pertussis adaptation to escape vaccine-induced immunity. Circulating bacteria differ genotypically from strains used in production of pertussis vaccine. Pertactin-deficient strains are highly prevalent in countries that use acellular vaccine (aP), suggesting strong aP-imposed selection of circulating bacteria. To corroborate this hypothesis, systematic studies on pertactin prevalence of infection in countries using whole-cell vaccine are needed. We provide pertussis epidemiologic data and molecular characterization of B. pertussis isolates from Buenos Aires, Argentina, during 2000–2017. This area used primary vaccination with whole-cell vaccine. Since 2002, pertussis case incidences increased at regular 4-year outbreaks; most cases were in infants <1 year of age. Of the B. pertussis isolates analyzed, 90.6% (317/350) contained the ptxP3-ptxA1-prn2-fim3-2 allelic profile. Immunoblotting and sequencing techniques detected only the 2 pertactin-deficient isolates. The low prevalence of pertactin-deficient strains in Argentina suggests that loss of pertactin gene expression might be driven by aP vaccine.

Data on the impact of the recently recommended maternal pertussis vaccination are promising, but still insufficient to universalise this approach. We thus compared the epidemiological data prior to the implementation of this vaccination strategy in Argentina (2012) with the figures reported after 2012. During that 2010-2016 period, two outbreaks occurred, one in 2011 and another in 2016. In the former, the incidence was 6.9/100 000 inhabitants and the case-fatality rate 2.6%. Thereafter, a decline in incidence was detected until 2014. During 2015 and 2016 an increase in the incidence transpired, but this rise was fortunately not accompanied by one in the case fatality ratio. Indeed, in 2016 the case fatality ratio was the lowest (0.6%). Moreover, during the 2016 outbreak, the incidence (3.9/100 000 inhabitants) and the case severity detected in the most vulnerable population (infants 0-2 months) were both lower than those in 2011. Consistent with this pattern, in 2016, in the most populated province of Argentina (Buenos Aires), the case percentage with laboratory-positive results indicating a high number of symptoms (59.1% of the total cases) diminished compared with that detected in the 2011 outbreak without maternal immunisation (71.9%). Using the mathematical model of pertussis transmission we previously designed, we assessed the effect of vaccination during pregnancy on infant incidence. From comparisons between the epidemiological data made through calculations, emerged the possibility that vaccinating women during pregnancy would benefit the infants beyond age 2 months, specifically in the 2-12-month cohort.

Background: The high COVID-19 dissemination rate demands active surveillance to identify asymptomatic, presymptomatic, and oligosymptomatic (APO) SARS-CoV-2-infected individuals. This is of special importance in communities inhabiting closed or semi-closed institutions such as residential care homes, prisons, neuropsychiatric hospitals, etc., where risk people are in close contact. Thus, a pooling approach—where samples are mixed and tested as single pools—is an attractive strategy to rapidly detect APO-infected in these epidemiological scenarios.Materials and Methods: This study was done at different pandemic periods between May 28 and August 31 2020 in 153 closed or semi-closed institutions in the Province of Buenos Aires (Argentina). We setup pooling strategy in two stages: first a pool-testing followed by selective individual-testing according to pool results. Samples included in negative pools were presumed as negative, while samples from positive pools were re-tested individually for positives identification.Results: Sensitivity in 5-sample or 10-sample pools was adequate since only 2 Ct values were increased with regard to single tests on average. Concordance between 5-sample or 10-sample pools and individual-testing was 100% in the Ct ≤ 36. We tested 4,936 APO clinical samples in 822 pools, requiring 86–50% fewer tests in low-to-moderate prevalence settings compared to individual testing.Conclusions: By this strategy we detected three COVID-19 outbreaks at early stages in these institutions, helping to their containment and increasing the likelihood of saving lives in such places where risk groups are concentrated.

The emergency of new SARS-CoV-2 variants that feature increased immune escape marks an urgent demand for better vaccines that will provide broader immunogenicity. Here, we evaluated the immunogenic capacity of vaccine candidates based on the recombinant trimeric spike protein (S) of different SARS-CoV-2 variants of concern (VOC), including the ancestral Wuhan, Beta and Delta viruses. In particular, we assessed formulations containing either single or combined S protein variants. Our study shows that the formulation containing the single S protein from the ancestral Wuhan virus at a concentration of 2µg (SW2-Vac 2µg) displayed in the mouse model the highest IgG antibody levels against all the three (Wuhan, Beta, and Delta) SARS-CoV-2 S protein variants tested. In addition, this formulation induced significantly higher neutralizing antibody titers against the three viral variants when compared with authorized Gam-COVID-Vac-rAd26/rAd5 (Sputnik V) or ChAdOx1 (AstraZeneca) vaccines. SW2-Vac 2µg was also able to induce IFN-gamma and IL-17, memory CD4 populations and follicular T cells. Used as a booster dose for schedules performed with different authorized vaccines, SW2-Vac 2µg vaccine candidate also induced higher levels of total IgG and IgG isotypes against S protein from different SARS-CoV-2 variants in comparison with those observed with homologous 3-dose schedule of Sputnik V or AstraZeneca. Moreover, SW2-Vac 2µg booster induced broadly strong neutralizing antibody levels against the three tested SARS-CoV-2 variants. SW2-Vac 2µg booster also induced CD4+ central memory, CD4+ effector and CD8+ populations. Overall, the results demonstrate that SW2-Vac 2 µg is a promising formulation for the development of a next generation COVID-19 vaccine.

Outer membrane vesicles (OMV) derived from Bordetella pertussis—the etiologic agent of the resurgent disease called pertussis—are safe and effective in preventing bacterial colonization in the lungs of immunized mice. Vaccine formulations containing those OMV are capable of inducing a mixed Th1/Th2/Th17 profile, but even more interestingly, they may induce a tissue-resident memory immune response. This immune response is recommended for the new generation of pertussis-vaccines that must be developed to overcome the weaknesses of current commercial acellular vaccines (second-generation of pertussis vaccine). The third-generation of pertussis vaccine should also deal with infections caused by bacteria that currently circulate in the population and are phenotypically and genotypically different [in particular those deficient in the expression of pertactin antigen, PRN(-)] from those that circulated in the past. Here we evaluated the protective capacity of OMV derived from bacteria grown in biofilm, since it was observed that, by difference with older culture collection vaccine strains, circulating clinical B. pertussis isolates possess higher capacity for this lifestyle. Therefore, we performed studies with a clinical isolate with good biofilm-forming capacity. Biofilm lifestyle was confirmed by both scanning electron microscopy and proteomics. While scanning electron microscopy revealed typical biofilm structures in these cultures, BipA, fimbria, and other adhesins described as typical of the biofilm lifestyle were overexpressed in the biofilm culture in comparison with planktonic culture. OMV derived from biofilm (OMVbiof) or planktonic lifestyle (OMVplank) were used to formulate vaccines to compare their immunogenicity and protective capacities against infection with PRN(+) or PRN(-) B. pertussis clinical isolates. Using the mouse protection model, we detected that OMVbiof-vaccine was more immunogenic than OMVplank-vaccine in terms of both specific antibody titers and quality, since OMVbiof-vaccine induced antibodies with higher avidity. Moreover, when OMV were administered at suboptimal quantity for protection, OMVbiof-vaccine exhibited a significantly adequate and higher protective capacity against PRN(+) or PRN(-) than OMVplank-vaccine. Our findings indicate that the vaccine based on B. pertussis biofilm-derived OMV induces high protection also against pertactin-deficient strains, with a robust immune response.

Maternal safety through pertussis vaccination and subsequent maternal–fetal-antibody transfer are well documented, but information on infant protection from pertussis by such antibodies and by subsequent vaccinations is scarce. Since mice are used extensively for maternal-vaccination studies, we adopted that model to narrow those gaps in our understanding of maternal pertussis immunization. Accordingly, we vaccinated female mice with commercial acellular pertussis (aP) vaccine and measured offspring protection against Bordetella pertussis challenge and specific-antibody levels with or without revaccination. Maternal immunization protected the offspring against pertussis, with that immune protection transferred to the offspring lasting for several weeks, as evidenced by a reduction (4–5 logs, p < 0.001) in the colony-forming-units recovered from the lungs of 16-week-old offspring. Moreover, maternal-vaccination-acquired immunity from the first pregnancy still conferred protection to offspring up to the fourth pregnancy. Under the conditions of our experimental protocol, protection to offspring from the aP-induced immunity is transferred both transplacentally and through breastfeeding. Adoptive-transfer experiments demonstrated that transferred antibodies were more responsible for the protection detected in offspring than transferred whole spleen cells. In contrast to reported findings, the protection transferred was not lost after the vaccination of infant mice with the same or other vaccine preparations, and conversely, the immunity transferred from mothers did not interfere with the protection conferred by infant vaccination with the same or different vaccines. These results indicated that aP-vaccine immunization of pregnant female mice conferred protective immunity that is transferred both transplacentally and via offspring breastfeeding without compromising the protection boostered by subsequent infant vaccination. These results—though admittedly not necessarily immediately extrapolatable to humans—nevertheless enabled us to test hypotheses under controlled conditions through detailed sampling and data collection. These findings will hopefully refine hypotheses that can then be validated in subsequent human studies.

Summary: Although titanium dioxide has a high surface area, it is not thermally stable and its surface area decreases strongly at high temperature due to phase transformation and crystal growth. To improve the thermal stability of titanium dioxide, the synthesis of mixed oxides can be an elegant approach. In this study different experimental variables for the synthesis and characterization of new titania‐silica mixed oxides intended to be used as fillers have been proposed. To manufacture the mixed oxides, different tetraethylortosilicate (TEOS)/Tetrabutyl orthotitanate (TBTi) mixtures in different ratio, ethanol as solvent, and acetic acid as catalyst were used via sol‐gel synthesis route. These oxides were characterized by transmission electron microscopy coupled with EDX analysis (TEM‐EDX), optical microscopy, X‐ray diffraction, textural properties, and pH measurements and wettability with liquids of different polarity.