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Science ◽  
2022 ◽  
Vol 375 (6577) ◽  
pp. 183-192
Author(s):  
Catherine J. Reynolds ◽  
Joseph M. Gibbons ◽  
Corinna Pade ◽  
Kai-Min Lin ◽  
Diana Muñoz Sandoval ◽  
...  

Immune imprinting For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immune responses to heterologous variants are influenced by a person’s infection history. Healthcare workers (HCWs) may be exposed to several doses and types of antigens, either by natural infection or by vaccination. Reynolds et al . studied a cohort of UK HCWs followed since March 2020. The immunological profiles of these people depended on how often the subject had encountered antigen and which variant was involved. Vaccine responses after infection were found to be less effective if the infection involved heterologous spike from a variant virus. Unfortunately, the N501Y spike mutation, found in many variants, seems to induce the regulatory T cell transcription factor FOXP3, indicating that the virus could subvert effective T cell function. Changes to antibody binding between variants also means that serology data using the Wuhan Hu-1 S1 receptor-binding domain sequence may not be a reliable measure of protection. —CA


Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 111
Author(s):  
Everett Webster ◽  
Kyra W. Seiger ◽  
Susan B. Core ◽  
Amanda L. Collar ◽  
Hannah Knapp-Broas ◽  
...  

An effective vaccine against Chlamydia trachomatis is urgently needed as infection rates continue to rise and C. trachomatis causes reproductive morbidity. An obligate intracellular pathogen, C. trachomatis employs a type 3 secretion system (T3SS) for host cell entry. The tip of the injectosome is composed of the protein CT584, which represents a potential target for neutralization with vaccine-induced antibody. Here, we investigate the immunogenicity and efficacy of a vaccine made of CT584 epitopes coupled to a bacteriophage virus-like particle (VLP), a novel platform for Chlamydia vaccines modeled on the success of HPV vaccines. Female mice were immunized intramuscularly, challenged transcervically with C. trachomatis, and assessed for systemic and local antibody responses and bacterial burden in the upper genital tract. Immunization resulted in a 3-log increase in epitope-specific IgG in serum and uterine homogenates and in the detection of epitope-specific IgG in uterine lavage at low levels. By contrast, sera from women infected with C. trachomatis and virgin controls had similarly low titers to CT584 epitopes, suggesting these epitopes are not systemically immunogenic during natural infection but can be rendered immunogenic by the VLP platform. C. trachomatis burden in the upper genital tract of mice varied after active immunization, yet passive protection was achieved when immune sera were pre-incubated with C. trachomatis prior to inoculation into the genital tract. These data demonstrate the potential for antibody against the T3SS to contribute to protection against C. trachomatis and the value of VLPs as a novel platform for C. trachomatis vaccines.


2022 ◽  
Vol 18 (1) ◽  
pp. e1010242
Author(s):  
Dina Khateeb ◽  
Tslil Gabrieli ◽  
Bar Sofer ◽  
Adi Hattar ◽  
Sapir Cordela ◽  
...  

In-depth analysis of SARS-CoV-2 quasispecies is pivotal for a thorough understating of its evolution during infection. The recent deployment of COVID-19 vaccines, which elicit protective anti-spike neutralizing antibodies, has stressed the importance of uncovering and characterizing SARS-CoV-2 variants with mutated spike proteins. Sequencing databases have allowed to follow the spread of SARS-CoV-2 variants that are circulating in the human population, and several experimental platforms were developed to study these variants. However, less is known about the SARS-CoV-2 variants that are developed in the respiratory system of the infected individual. To gain further insight on SARS-CoV-2 mutagenesis during natural infection, we preformed single-genome sequencing of SARS-CoV-2 isolated from nose-throat swabs of infected individuals. Interestingly, intra-host SARS-CoV-2 variants with mutated S genes or N genes were detected in all individuals who were analyzed. These intra-host variants were present in low frequencies in the swab samples and were rarely documented in current sequencing databases. Further examination of representative spike variants identified by our analysis showed that these variants have impaired infectivity capacity and that the mutated variants showed varied sensitivity to neutralization by convalescent plasma and to plasma from vaccinated individuals. Notably, analysis of the plasma neutralization activity against these variants showed that the L1197I mutation at the S2 subunit of the spike can affect the plasma neutralization activity. Together, these results suggest that SARS-CoV-2 intra-host variants should be further analyzed for a more thorough characterization of potential circulating variants.


Author(s):  
Giacomo Maria Viani ◽  
Patrizia Pedrotti ◽  
Romano Seregni ◽  
Brucato Antonio

Abstract Background Whereas effusive-constrictive pericarditis can rarely occur in COVID-19, to date no cases of effusive-constrictive pericarditis related to SARS-CoV2 vaccine have been documented. Case summary A 59-year-old caucasian man presented to our emergency department with effusive-constrictive pericarditis. Symptoms occurred shortly after the second dose of BNT162b2 (Comirnaty) vaccine. No other etiological causes were identified. Guidelines directed therapy for acute pericarditis was implemented, with clinical benefit. Discussion Systemic inflammatory response to COVID-19 can rarely trigger pericarditis. In our case a strong temporal relation between the second dose of BNT162b2 vaccine and symptoms occurrence was documented, indicating a possible rare adverse reaction to the vaccine, similarly to natural infection. Further research is needed to confirm a causal relationship.


Author(s):  
R C S Guimarães ◽  
E F Marialva ◽  
J A Feijó ◽  
J W Pereira-Silva ◽  
K M Martins-Campos ◽  
...  

Abstract Trypanosomatids (Kinetoplastida:Trypanosomatidae) protozoa are a diverse group of obligate parasites. The genera Trypanosoma and Leishmania are the most studied because of their medical importance. This work aims to evaluate the effects of anthropization processes on the composition of the phlebotomine sand fly fauna and the natural infection by Trypanosomatids, with emphasis on Leishmania. At all 3,186 sand flies were collected, distributed in 13 genera and 52 species, being Ny. umbratilis the most abundant species. There was no difference in the diversity between canopy and soil environments. The species abundance and richness were higher in the forest environment while species diversity and evenness were highest in the forest edge. The ITS1 region was used by PCR-RFLP to identify the fragment profiles of Leishmania species, followed by genetic sequencing. Here were analyzed 100 pools of female sand flies, being six positive for DNA parasite. PCR-RFLP fragment patterns similar to Endotrypanum sp. were observed in Nyssomyia anduzei, Psychodopygus amazonensis and Lutzomyia gomezi, and those fragments similar to Leishmania (Leishmania) amazonensis were observed in Bichromomyia flaviscutellata. ITS1 sequencing confirmed the presence of Leishmania sp. in Bi. flaviscutellata, and Leishmania (Viannia) naiffi in Ny. anduzei, Psychodopygus amazonensis, and Lu. gomezi. This is the first record of Lu. gomezi and Ps. amazonensis infection by L. naiffi in the State of Amazonas. These results show the trypanosomatid infection in sandflies from different landscapes in a rural settlement, and the finding of species infected with L.(V.) naiffi suggest that they can develop a role in the transmission cycle of leishmaniasis.


npj Vaccines ◽  
2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Lisa H. Tostanoski ◽  
Abishek Chandrashekar ◽  
Shivani Patel ◽  
Jingyou Yu ◽  
Catherine Jacob-Dolan ◽  
...  

AbstractSARS-CoV-2 Spike-specific binding and neutralizing antibodies, elicited either by natural infection or vaccination, have emerged as potential correlates of protection. An important question, however, is whether vaccine-elicited antibodies in humans provide direct, functional protection from SARS-CoV-2 infection and disease. In this study, we explored directly the protective efficacy of human antibodies elicited by Ad26.COV2.S vaccination by adoptive transfer studies. IgG from plasma of Ad26.COV2.S vaccinated individuals was purified and transferred into naïve golden Syrian hamster recipients, followed by intra-nasal challenge of the hamsters with SARS-CoV-2. IgG purified from Ad26.COV2.S-vaccinated individuals provided dose-dependent protection in the recipient hamsters from weight loss following challenge. In contrast, IgG purified from placebo recipients provided no protection in this adoptive transfer model. Attenuation of weight loss correlated with binding and neutralizing antibody titers of the passively transferred IgG. This study suggests that Ad26.COV2.S-elicited antibodies in humans are mechanistically involved in protection against SARS-CoV-2.


2022 ◽  
Author(s):  
Krishna Mohan Vadrevu ◽  
Brunda Ganneru ◽  
Siddharth Reddy ◽  
Harsh Jogdand ◽  
Raju Dugyala ◽  
...  

Background: Neutralising antibody responses to SARS-CoV-2 vaccines have been reported to decline within 6 months of vaccination, particularly against Variants of Concern (VOC). We assessed the immunogenicity and safety of a booster dose of BBV152 administered 6 months after the second of a two-dose primary vaccination series. Methods: In an ongoing phase 2 trial (ClinicalTrials.gov: NCT04471519) the protocol was amended after six months to re-consent and randomise 184 previously vaccinated participants to receive a third dose of vaccine or placebo on Day 215. The primary outcome was to measure neutralising antibody titres by plaque-reduction neutralisation test (PRNT50) four weeks after the booster; safety as serious adverse events (SAE) was the key secondary outcome. Findings: Four weeks after a second BBV152 vaccination geometric mean titres (GMTs) of neutralising antibodies were 197.0 PRNT50 (95% CI: 155.6,249.4); this level declined to 23.9 PRNT50 (14.0,40.6) six months later, with a seroconversion rate of 75.4% (95% CI: 68.4,81.6). Four weeks after booster vaccination the GMT increased on Day 243 to 746.6 PRNT50 (514.9,1081) compared with 100.7 PRNT50 (43.6,232.6) in the placebo group. Corresponding seroconversion rates were 98.7% (92.8,99.9) and 79.8% (69.6,87.8). Increased titres in the placebo group were attributed to natural infection as the study was conducted during the second wave of COVID-19 in India. PRNT50 titres against the SARS-CoV-2 variants increased Alpha (32.6 fold), Beta (161.0 fold), Delta (264.7 fold), and Delta plus (174.2 fold) after the booster vaccination. We found that vaccine induces both memory B and T cells with a distinct AIM+ specific CD4+T central and effector memory phenotype, including CD8+ TEMRA phenotype. Reactogenicity after vaccine and placebo was minimal and comparable, and no SAEs were reported. Interpretation: Six months after a two dose BBV152 vaccination series cell mediated immunity and neutralising antibodies to both homologous (D614G) and heterologous strains (Alpha, Beta, Delta and Delta plus) persisted above baseline, although the magnitude of the responses had declined. Neutralising antibodies against homologous and heterologous SARS-CoV-2 variants increased 19 to 97 fold after a third vaccination. Booster BBV152 vaccination is safe and may be necessary to ensure persistent immunity to prevent breakthrough infections.


2022 ◽  
Vol 66 (6) ◽  
pp. 399-408
Author(s):  
S. S. Zainutdinov ◽  
G. F. Sivolobova ◽  
V. B. Loktev ◽  
G. V. Kochneva

Mucosal immunity is realized through a structural and functional system called mucose-associated lymphoid tissue (MALT). MALT is subdivided into parts (clusters) depending on their anatomical location, but they all have a similar structure: mucus layer, epithelial tissue, lamina propria and lymphoid follicles. Plasma cells of MALT produce a unique type of immunoglobulins, IgA, which have the ability to polymerize. In mucosal immunization, the predominant form of IgA is a secretory dimer, sIgA, which is concentrated in large quantities in the mucosa. Mucosal IgA acts as a first line of defense and neutralizes viruses efficiently at the portal of entry, preventing infection of epithelial cells and generalization of infection. To date, several mucosal antiviral vaccines have been licensed, which include attenuated strains of the corresponding viruses: poliomyelitis, influenza, and rotavirus. Despite the tremendous success of these vaccines, in particular, in the eradication of poliomyelitis, significant disadvantages of using attenuated viral strains in their composition are the risk of reactogenicity and the possibility of reversion to a virulent strain during vaccination. Nevertheless, it is mucosal vaccination, which mimics a natural infection, is able to induce a fast and effective immune response and thus help prevent and possibly stop outbreaks of many viral infections. Currently, a number of intranasal vaccines based on a new vector approach are successfully undergoing clinical trials. In these vaccines, the safe viral vectors are used to deliver protectively significant immunogens of pathogenic viruses. The most tested vector for intranasal vaccines is adenovirus, and the most significant immunogen is SARSCoV-2 S protein. Mucosal vector vaccines against human respiratory syncytial virus and human immunodeficiency virus type 1 based on Sendai virus, which is able to replicate asymptomatically in cells of bronchial epithelium, are also being investigated.


2022 ◽  
Author(s):  
Fanglei Zuo ◽  
Hassan Abolhassani ◽  
Likun Du ◽  
Antonio Piralla ◽  
Federico Bertoglio ◽  
...  

Abstract Background There has been an unprecedented global effort to produce safe and effective vaccines against SARS-CoV-2. However, production challenges, supply shortages and unequal global reach, together with an increased number of breakthrough infections due to waning of immunity and the emergence of new variants of concern (VOC), have prolonged the pandemic. To boost the immune response, several heterologous vaccination regimes have been tested and have shown increased antibody responses compared to homologous vaccination. Here we evaluated the effect of mRNA vaccine booster on immunogenicity in individuals who had been vaccinated with two doses of inactivated vaccines. Methods The levels of specific antibodies against the receptor-binding domain (RBD) of the spike protein from wild-type virus and the Beta, Delta and Omicron variants were measured in healthy individuals who had received two doses of homologous inactivated (BBIBP-CorV or CoronoVac) or mRNA (BNT162b2 or mRNA-1273) vaccines, and in donors who were given an mRNA vaccine boost after two doses of either vaccine. Pre-vaccinated healthy donors, or individuals who had been infected and subsequently received the mRNA vaccine were also included as controls. In addition, specific memory B and T cell responses were measured in a subset of samples. Results A booster dose of an mRNA vaccine significantly increased the specific antibody response to the wild-type and VOCs including Omicron (by 14-fold), in individuals who had previously received two doses of inactivated vaccines. The levels of specific antibodies in the heterologous vaccination group were similar to those in individuals receiving a third dose of homologous mRNA vaccines or boosted with mRNA vaccine after natural infection. Furthermore, this heterologous vaccination regime significantly improved the specific memory B and T cell responses. Conclusions Heterologous prime-boost immunization with inactivated vaccine followed by an mRNA vaccine boost markedly increased the levels of specific antibodies and B and T cell responses and may thus increase protection against emerging SARS-CoV-2 variants including Omicron.


2022 ◽  
Author(s):  
Guruprasad R Medigeshi ◽  
Gaurav Batra ◽  
Deepika Rathna Murugesan ◽  
Ramachandran Thiruvengadam ◽  
Souvick Chattopadhyay ◽  
...  

Background: Rapid expansion of the omicron SARS-CoV-2 variant of concern despite extensive vaccine coverage might be related to decreased neutralising ability of vaccine induced antibodies. The neutralising ability of different vaccines with or without natural SARS-CoV-2 infection against omicron is however not well known. Methods: We tested the ability of vaccine and natural infection induced antibodies to neutralise omicron variant in a live virus neutralisation assay. Four groups of individuals were included: (i) complete vaccination with ChAdOx1 nCoV-19 (n=20), (ii) complete vaccination with ChAdOx1 nCoV-19 plus prior SARS-CoV-2 infection during the delta variant driven surge (n=20), (iii) complete vaccination with inactivated whole virus vaccine (BBV152) (n=20), (iv) complete vaccination with BBV152 plus prior SARS-CoV-2 infection (n=20). Primary outcome was fold-change in the virus neutralisation ability of plasma against the omicron variant compared with ancestral and delta variant. Findings: The neutralisation geometric mean titre (GMT) was 384 (95% CI: 662, 223) against the ancestral virus with BBV152 vaccination alone and 383 (95% CI: 709, 207) with ChAdOx1 nCov-19 vaccination alone. The corresponding values for hybrid immunity groups were 795 (95% CI: 1302, 486) and 1424 (95% CI: 2581,786) respectively. Against the omicron variant, only 5 out of 20 in both BBV152 and ChAdOx1 nCoV-19 vaccine only groups, 5 out of 19 in BBV152 plus SARS-CoV-2 infection group, and 9 out of 20 in ChAdOx1 nCoV-19 plus SARS-CoV-2 infection group exhibited neutralisation titres above the lower limit of quantification (1:20). The 50% neutralization titre against ancestral strain and omicron demonstrated strong correlation with anti-RBD IgG levels [Pearson r: 0.94 (0.91, 0.96) p: <0.001 and 0.92 (0.88, 0.95) p:<0.001 respectively]. Interpretation: Omicron variant shows significant reduction in neutralising ability of both vaccine induced and hybrid immunity induced antibodies which might explain immune escape and high transmission even in the presence of widespread vaccine coverage.


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