UNASSIGNED: Some studies suggest that the monovalent mRNA-1273 vaccine is more effective than BNT162b2 in producing higher levels of antibodies. However, limited data are available, and the methods used are not directly comparable.
UNASSIGNED: Blood samples were obtained before the booster (third dose) and after 14, 90, and 180 days in two similar cohorts who received the original BNT162b2 or mRNA-1273 vaccine designed to target wild type SARS-CoV-2. The aim of our study is to compare their effectiveness by assessing the levels of binding and neutralizing antibodies specifically against each of the BA.1 variant, BA.5 variant, and the XBB.1.5 subvariant.
UNASSIGNED: Once the peak was reached after two weeks, a drastic decline in binding and neutralizing antibodies was observed up to 6 months after the homologous booster administration. The humoral response was however more sustained with the mRNA-1273 booster, with half-lives of 167, 55, and 48 days for binding, BA.1, and BA.5 neutralizing antibodies compared to 144, 30, and 29 days for the BNT162b2 booster, respectively. Compared to the BA.1 variant, the neutralizing capacity was significantly decreased at 6 months with the BA.5 variant (fold-decrease: 1.67 to 3.20) and the XBB.1.5. subvariant (fold-decrease: 2.86 to 5.48).
UNASSIGNED: Although the decrease in the humoral response was observed with both mRNA vaccines over time, a more sustained response was observed with the mRNA-1273 vaccine. Moreover, the emergence of Omicron-based variants causes a reduced neutralizing capacity, notably with the XBB.1.5. subvariant. The administration of subsequent boosters would therefore be needed to restore a sufficiently high neutralizing response.

BACKGROUND: Vaccination is one of the most effective medical interventions to prevent infectious diseases. The introduction of vaccines against coronavirus acute respiratory syndrome 2 (SARS-CoV-2) was aimed at preventing severe illness and death due to coronavirus disease 2019 (COVID-19). Solid organ transplant recipients (SOTRs) are at high risk of infection with SARS-CoV-2 and serious effects associated with COVID-19, mainly due to the use of immunosuppressive therapies, which further cause suboptimal response to COVID-19 vaccination.
OBJECTIVE: We aimed to compare post-vaccination response to BNT162b2 in kidney-pancreas transplant recipient, specifically in immunocompetent individuals, over two years of simultaneous monitoring.
METHODS: To determine the humoral response, the levels of the IgG and IgA anti-S1 antibodies were measured. To assess the cellular response to SARS-CoV-2, the released IFN-γ-S1 was determinate.
CONCLUSIONS: After primary vaccination, compared to immunocompetent subjects, SOTR showed lower seroconversion for both antibody classes. Only the additional dose produced antibodies at the level reached by the control group after the baseline vaccination. During the monitored period, SOTR did not achieve a positive cellular response in contrast to immunocompetent individuals, so in order to obtain longer protection, including immune memory, the adoption of booster doses of the vaccine should be considered.

UNASSIGNED: The impact of corticosteroids on humoral responses in coronavirus disease 2019 (COVID-19) survivors during the acute phase and subsequent 6-month period remains unknown. This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset.
UNASSIGNED: We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020, which involved adults hospitalized with severe COVID-19 (LOTUS, ChiCTR2000029308). Antibody samples were collected from 192 patients during hospitalization, and kinetic antibodies were monitored at all available time points after recruitment. Additionally, plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit. The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group.
UNASSIGNED: From illness onset to day 30, the median antibody titre areas under the receiver operating characteristic curve (AUCs) of nucleoprotein (N), spike protein (S), and receptor-binding domain (RBD) immunoglobulin G (IgG) were significantly lower in the corticosteroids group. The AUCs of N-, S-, and RBD-IgM as well as neutralizing antibodies (NAbs) were numerically lower in the corticosteroids group compared with the non-corticosteroid group. However, peak titres of N, S, RBD-IgM and -IgG and NAbs were not influenced by corticosteroids. During 6-month follow-up, we observed a delayed decline for most binding antibodies, except N-IgM (β -0.05, 95% CI [-0.10, 0.00]) in the corticosteroids group, though not reaching statistical significance. No significant difference was observed for NAbs. However, for the half-year seropositive rate, corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-, S-, and RBD-IgG or NAbs. Additionally, corticosteroids group showed a trend towards delayed viral clearance compared with the non-corticosteroid group, but the results were not statistically significant (adjusted hazard ratio 0.71, 95% CI 0.50-1.00; P = 0.0508).
UNASSIGNED: Our findings suggested that corticosteroid therapy was associated with impaired initiation of the antibody response but this did not compromise the peak titres of binding and neutralizing antibodies. Throughout the decay phase, from the acute phase to the half-year follow-up visit, short-term and low-dose corticosteroids did not significantly affect humoral responses, except for accelerating the waning of short-lived antibodies.

The COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Although our understanding of the pandemic has improved significantly since the beginning, the natural history of COVID-19 and its impacts on under-represented populations, such as Indigenous people from America, remain largely unknown. We performed a retrospective serological survey with two Brazilian Indigenous populations (n=624), Tupiniquim and Guarani-Mbyá. Samples were collected between September 2020 and July 2021: a period comprising the dissemination of SARS-CoV-2 variants and the beginning of COVID-19 vaccination in Brazil. Seroconversions against S and N antigens were assessed using three different commercially available ELISA kits. Samples were also used to assess the prevalence of tuberculosis (TB) in the same population (n=529). Seroconversion against SARS-CoV-2 antigens was considered positive if at least one of the three ELISA kits detected levels of specific antibodies above the threshold specified by the manufacturer. In this sense, we report 56.0% (n=349/623) of seroconverted individuals. Relative seroconversion peaked after introduction of the Coronavac vaccine in February 2021. Vaccination increased the production of anti-S IgG from 3.9% to 48.6%. Our results also indicated that 11.0% (n=46/417) of all individuals were positive for TB. Seroconversion to SARS-CoV-2 was similar between individuals with positive tuberculosis test results to those with negative test results. Most vaccinated individuals seroconverted to SARS-CoV-2, indicating that Coronavac may be as protective in individuals from these indigenous groups as observed in the general Brazilian population. COVID-19 severity was minimal regardless of incomplete vaccine coverage, suggesting that vaccination may not be the only factor protecting individuals from severe COVID-19. Tuberculosis is highly prevalent and not associated with increased seroconversion to SARS-CoV-2.

HIV-1 has an antisense gene overlapping env that encodes the ASP protein. ASP functions are still unknown, but it has been associated with gp120 in the viral envelope and membrane of infected cells, making it a potential target for immune response. Despite this, immune response patterns against ASP are poorly described and can be influenced by the high genetic variability of the env gene. To explore this, we analyzed 100k HIV-1 ASP sequences from the Los Alamos HIV sequence database using phylogenetic, Shannon entropy (Hs), and logo tools to study ASP variability in worldwide and Brazilian sequences from the most prevalent HIV-1 subtypes in Brazil (B, C, and F1). Data obtained in silico guided the design and synthesis of 15-mer overlapping peptides through spot synthesis on cellulose membranes. Peptide arrays were screened to assess IgG and IgM responses in pooled plasma samples from HIV controllers and individuals with acute or recent HIV infection. Excluding regions with low alignment accuracy, several sites with higher variability (Hs > 1.5) were identified among the datasets (25 for worldwide sequences, 20 for Brazilian sequences). Among sites with Hs < 1.5, sequence logos allowed the identification of 23 other sites with subtype-specific signatures. Altogether, amino acid variations with frequencies > 20% in the 48 variable sites identified were included in 92 peptides, divided into 15 sets, representing near full-length ASP. During the immune screening, the strongest responses were observed in three sets, one in the middle and one at the C-terminus of the protein. While some sets presented variations potentially associated with epitope displacement between IgG and IgM targets and subtype-specific signatures appeared to impact the level of response for some peptides, signals of cross-reactivity were observed for some sets despite the presence of B/C/F1 signatures. Our data provides a map of ASP regions preferentially targeted by IgG and IgM responses. Despite B/C/F1 subtype signatures in ASP, the amino acid variation in some areas preferentially targeted by IgM and IgG did not negatively impact the response against regions with higher immunogenicity.

We recently showed that an adapted SARS-CoV-2 vaccine with wildtype and BA.4/BA.5 Omicron subtype epitopes induced a broad short-term immune response in hemodialysis patients. Antibodies with protective capacity were boosted significantly after a follow-up period of 3 weeks following a fifth vaccine dose. However, data on the longevity of the humoral response after bivalent vaccination are lacking but urgently needed to make recommendations for further booster vaccinations in this patient group. This study is an extension of our previously published data including 40 patients on hemodialysis with a follow-up period of 12 months after an adapted booster vaccine dose. We performed a detailed characterization of humoral immune responses and assessed breakthrough infections. In addition, the severity of breakthrough infections was assessed using an established grading system. Anti-S1 IgG and surrogate neutralizing antibodies significantly decreased during the period of 12 months (p < 0.01 and p < 0.001, respectively). Live-virus neutralizing antibodies against the wildtype and the BA.5 subtype also significantly decreased over time (p < 0.01 and p < 0.01, respectively). However, even 12 months after administration of the adapted vaccine dose, all 40/40 (100%) of hemodialysis patients showed detectable SARS-CoV-2 wildtype neutralization activity, with 35/40 (88%) also exhibiting detectable BA.5 subtype neutralization activity. During follow-up, 13/40 (33%) patients contracted a SARS-CoV-2 breakthrough infection, among which 12 cases were categorized as asymptomatic or mild, while only 1 case was classified as moderate disease activity. Thus, bivalent booster vaccination seems to induce a sustained immune response in hemodialysis patients over a period of 12 months with breakthrough infections occurring frequently but predominantly manifesting as asymptomatic or mild.

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) causes reproductive failure and respiratory symptoms, leading to huge economic losses for the pig farming industry. Although several vaccines against PRRSV are available in the market; they show an overall low efficacy, and several countries have the need for vaccines covering the local, circulating variants. This project aims at developing a new chimeric antigen targeting specific epitopes from PRRSV and evaluating two test adjuvants to formulate a vaccine candidate. The test antigen was called LTB-PRRSV, which was produced recombinantly in Escherichia coli and consisted of the heat labile enterotoxin B subunit from E. coli (LTB) and four epitopes from PRRSV. LTB-PRRSV was rescued as inclusion bodies and methods for its solubilization, IMAC-based purification, and refolding were standardized, leading to mean yields of 18 mg of pure protein per liter culture. Layered double hydroxides (LDH) have been used as vaccine adjuvants given their biocompatibility, low cost, and positive surface charge that allows an efficient adsorption of negatively charged biomolecules. Therefore, LDH were selected as delivery vehicles of LTB-PRRSV. Pure LTB-PRRSV was adsorbed onto LDH by incubation at different LDH:LTB-PRRSV mass ratios (1:0.25, 1:0.5, 1:1, and 1:2) and at pH 9.5. The best adsorption occurred with a 1:2 mass ratio, and in a sucrose-tween solution. The conjugates obtained had a polydispersity index of 0.26, a hydrodynamic diameter of 192 nm, and a final antigen concentration of 64.2 μg/mL. An immunogenicity assessment was performed by injecting mice with LDH:LTB-PRRSV, Alum/LTB-PRRSV, or LTB-PRRSV in a scheme comprising three immunizations at two-week intervals and two dose levels (1 and 5 μg). LTB-PRRSV was capable of inducing strong humoral responses, which lasted for a longer period when LDH was used as the delivery vehicle/adjuvant. The potential of LDH to serve as an attractive carrier for veterinary vaccines is discussed.

This study assessed humoral and T cell-mediated immune responses to the BNT162b2 vaccine in orthotopic liver transplant (OLT) and lung transplant (LUT) recipients who received three doses of the vaccine from March 2021 at our institution. Serum samples were collected 60 days post-second and third dose to quantify antibodies against the spike region of SARS-CoV-2 while whole blood samples were collected to analyze the SARS-CoV-2-specific T-cell response using an IFN-γ ELISpot assay. We enrolled 244 OLT and 120 LUT recipients. The third dose increased antibody titres in OLT recipients (from a median value of 131 after the second dose to 5523 IU/mL, p < 0.001) and LUT recipients (from 14.8 to 1729 IU/mL, p < 0.001). T-cell response also increased in OLT recipients (from 8.5 to 23 IFN-γ SFU per 250,000 PBMC, p < 0.001) and LUT recipients (from 8 to 15 IFN-γ SFU per 250,000 PBMC, p < 0.001). A total of 128 breakthrough infections were observed: two (0.8%) OLT recipients were hospitalized due to COVID-19 and one died (0.4%); among LUT recipients, seven were hospitalized (5.8%) and two patients died (1.7%). In conclusion, the three-dose schedule of the BNT162b2 vaccine elicited both humoral and T cell-mediated responses in solid organ transplant recipients. The risk of severe COVID-19 post-vaccination was low in this population.

Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8+ T cell responses in 26 COVID-19 patients diagnosed with severe disease, initially (1 month) and long-term (10 months), and in a cohort of 32 vaccinated healthcare workers without previous SARS-CoV-2 infection. We used peptide-human leukocyte antigen (pHLA) dextramers recognizing 26 SARS-CoV-2-derived epitopes of viral and other non-structural proteins. Most patients responded to at least one of the peptides studied, mainly derived from non-structural ORF1ab proteins. After 10 months follow-up, CD8+ T cell responses were maintained at long term and reaction against certain epitopes (A*01:01-ORF1ab1637) was still detected and functional, showing a memory-like phenotype (CD127+ PD-1+). The total number of SARS-CoV-2-specific CD8+ T cells was significantly associated with protection against long COVID in these patients. Compared with vaccination, infected patients showed a less effective immune response to spike protein-derived peptides restricted by HLA. So, the A*01:01-S865 and A*24:02-S1208 dextramers were only recognized in vaccinated individuals. We conclude that initial SARS-CoV-2-specific CD8+ T cell response could be used as a marker to understand the evolution of severe disease and post-acute sequelae after SARS-CoV-2 infection.

Novel mechanisms of COVID-19 vaccines raised concern about their potential immunogenicity in patients with rheumatoid arthritis (RA) undergoing immunomodulatory treatments. We designed a retrospective single-center study to investigate their effectiveness and safety in this population, analyzing data from the first vaccination program (December 2020-October 2021). Inclusion criteria were availability of post-vaccination serology and a minimum subsequent follow-up of 6 months. Binding antibody units (BAU/mL) ≥ 7.1 defined an adequate serological response. Post-vaccine COVID-19 incidence and its timing since vaccination, adverse events (AEs), and RA flares were recorded. Adjusted logistic and linear multivariate regression analyses were carried out to identify factors associated with vaccine response. We included 118 patients (87.2% women, age 65.4 ± 11.6 years, evolution 12.0 ± 9.6 years), of whom 95.8% had a complete vaccination schedule. Adequate humoral immunogenicity was achieved in 88.1% of patients and was associated with previous COVID-19 and mRNA vaccines, whereas smoking, aCCP, age, and DMARDs exerted a negative impact. Post-vaccine COVID-19 occurred in 18.6% of patients, a median of 6.5 months after vaccination. Vaccine AE (19.5%) and RA flares (1.7%) were mostly mild and inversely associated with age. Our results suggest that COVID-19 vaccines induce adequate humoral immunogenicity, with an acceptable safety profile in RA patients.