The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or infection. Despite the global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc effector mechanisms. Here, we probed the ability of vaccine-induced antibodies to drive Fc effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant receptor binding domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of RBD-specific antibody Fcγ receptor (FcγR) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific FcγR2a and FcγR3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein–specific antibodies exhibited persistent but reduced binding to FcγRs across all three vaccines, although higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of FcγR2a and FcγR3a binding antibodies and maintenance of Spike protein–specific antibody-dependent natural killer cell activation. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein–specific antibodies continue to drive Fc effector functions, suggesting a capacity for extraneutralizing antibodies to contribute to disease control.

The durability of circulating neutralizing antibody (nAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their boosting by vaccination remains to be defined. We show that outpatient and hospitalized SARS-CoV-2 seropositive individuals mount a robust neutralizing antibody (nAb) response that peaks at days 23 and 27 post-symptom onset, respectively. Although nAb titers remained higher in hospitalized patients, both study groups showed long-lasting nAb responses that can persist for up to 12 months after natural infection. These nAb responses in previously seropositive individuals can be significantly boosted through immunization with two doses of the CoronaVac (Sinovac) or one dose of the BNT162b2 (BioNTech/Pfizer) vaccines, suggesting a substantial induction of B cell memory responses. Noteworthy, three obese previously seropositive individuals failed to mount a booster response upon vaccination, warranting further studies in this population. Immunization of naïve individuals with two doses of the CoronaVac vaccine or one dose of the BNT162b2 vaccine elicited similar levels of nAbs compared to seropositive individuals 4.2 to 13.3 months post-infection with SARS-CoV-2. Thus, this preliminary evidence suggests that both, seropositive and naïve individuals, require two doses of CoronaVac to ensure the induction of robust nAb titers.

Pathogenicity island excision is a phenomenon that occurs in several Salmonella enterica serovars and other members of the family Enterobacteriaceae. ROD21 is an excisable pathogenicity island found in the chromosome of S. Enteritidis, S. Dublin and S. Typhi among others, which contain several genes encoding virulence-associated proteins. Excision of ROD21 may play a role in the ability of S. Enteritidis to cause a systemic infection in mice. Our previous studies have shown that Salmonella strains unable to excise ROD21 display a reduced ability to colonize the liver and spleen. In this work, we determined the kinetics of ROD21 excision in vivo in C57BL/6 mice and its effect on virulence. We quantified bacterial burden and excision frequency in different portions of the digestive tract and internal organs throughout the infection. We observed that the frequency of ROD21 excision was significantly increased in the bacterial population colonizing mesenteric lymph nodes at early stages of the infective cycle, before 48 hours post-infection. In contrast, excision frequency remained very low in the liver and spleen at these stages. Interestingly, excision increased drastically after 48 h post infection, when intestinal re-infection and mortality begun. Moreover, we observed that the inability to excise ROD21 had a negative effect on S. Enteritidis capacity to translocate from the intestine to deeper organs, which correlates with an abnormal transcription of invA in the S. Enteritidis strain unable to excise ROD21. These results suggest that excision of ROD21 is a genetic mechanism required by S. Enteritidis to produce a successful invasion of the intestinal epithelium, a step required to generate systemic infection in mice. Salmonella is a bacterial genus that causes foodborne illnesses worldwide. The ability of Salmonella to cause disease is related to the presence of Pathogenicity Islands (PAIs), which are clusters of genes within the bacterial chromosome that are involved in virulence. Interestingly, some PAIs excise and re-integrate into the bacterial chromosome, which is a process probably involved in the capacity of Salmonella to cause infection in their hosts. Here we show that the excision of Region of Difference 21 (ROD21), one of the excisable PAIs within the genome of Salmonella enterica serovar Enteritidis, occurs with high frequency in the mesenteric lymph node at early stages of infection, suggesting that excision is required by S. Enteritidis to reach this organ from the intestinal tract. Accordingly, S. Enteritidis strains unable to excise ROD21 are unable to invade intestinal host cells, delaying the infective cycle and showing attenuated virulence. We propose that ROD21 excision in vivo is required by S. Enteritidis to cross the intestinal barrier, a fundamental step to further colonize deep organs, due to modulation of virulence genes transcription. Thus, ROD21 excision may play an important role in the capacity of the bacteria to cause a successful systemic infection in the mouse. Our data suggest that the excision of PAIs is a mechanism used by Salmonella and probably other Gram-negative enterobacteria to modulate the expression of virulence genes and may provide insights to design novel therapies to control the infection caused by these pathogens.

Since the first report of SARS-CoV-2 infection in humans, the virus has mutated to develop new viral variants with higher infection rates and more resistance to neutralization by antibodies elicited after natural SARS-CoV-2 infection or by vaccines. Therefore, rapid identification of viral variants circulating in the population is crucial for epidemiological assessment and efforts to contain the resurgence of the pandemic. Between January and November 2021, we performed a large variant RT-qPCR-based screening of mutations in the spike protein of 1851 SARS-CoV-2-positive samples derived from outpatients from the UC-Christus Health Network in Chile. In a portion of samples (n = 636), we validated our RT-qPCR-pipeline by WGS, obtaining a 99.2% concordance. Our results indicate that from January to March 2021 there was a dominance of non-identifiable variants by the RT-qPCR-based screening; however, throughout WGS we were able to identify the Lambda (C.37) variant of interest (VOI). From March to July, we observed the rapid emergence of mutations associated with the Gamma variant (P.1), which was quickly replaced by the appearance of a combination of samples harboring mutations associated with the Delta variant (B.1.617.2), which predominated until the end of the study. Our results highlight the applicability of cost-effective RT-qPCR-based screening of mutations associated with known variants of concern (VOC), VOI and variants under monitoring (VUM) of SARS-CoV-2, being a rapid and reliable tool that complements WGS-based surveillance.

The ongoing extinction crisis, driven by human activity, poses a significant threat to seabirds and it’s especially relevant in highly valuable environments such as Antarctica. Among these threats, seabirds face the risk of local extinctions due to emerging infectious diseases like the Highly Pathogenic Avian Influenza Virus (HPAIV).Progressive spread of HPAIV A/H5N1 outbreaks across South America and the sub-Antarctic islands have been detected, reaching the northern regions of the West Antarctic Peninsula (WAP) during the 2023-2024 season. Here we conducted a comprehensive epidemiological survey conducted on sixteen seabird nesting localities along the WAP from November 2024 to January 2025 to assess the health status of the Antarctic seabirds and detect the presence of HPAIV. We observed unusual mortalities among nesting populations of skuas, with a total of 35 deaths skuas recorded along the WAP and beyond the Antarctic Polar Circle, including Important bird breeding areas around Margarita Bay. HPAIV A/H5 was confirmed in all dead skuas sampled (n=11), from six different locations. This finding represents the southernmost record of seabird mortality in Antarctica related to HPAIV to date. The expansion of HPAIV observed here raises concerns about further spread of avian flu out the Antarctic Peninsula, potentially leading to increased mortality rates in the Antarctic bird populations. These findings are relevant for the assessment of the general health status of Antarctic seabird populations and provide a baseline for the continuous monitoring of the HPAIV spread in avian species during the next breeding seasons.