Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies.

Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection, including against avian H5N1 viruses, in vivo. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48 hr post infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains.

Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response.

Cell fate decisions during early B cell activation determine the outcome of responses to pathogens and vaccines. We examined the early B cell response to T-dependent antigen in mice by single-cell RNA sequencing. Early after immunization, a homogeneous population of activated precursors (APs) gave rise to a transient wave of plasmablasts (PBs), followed a day later by the emergence of germinal center B cells (GCBCs). Most APs rapidly exited the cell cycle, giving rise to non-GC-derived early memory B cells (eMBCs) that retained an AP-like transcriptional profile. Rapid decline of antigen availability controlled these events; provision of excess antigen precluded cell cycle exit and induced a new wave of PBs. Fate mapping revealed a prominent contribution of eMBCs to the MBC pool. Quiescent cells with an MBC phenotype dominated the early response to immunization in primates. A reservoir of APs/eMBCs may enable rapid readjustment of the immune response when failure to contain a threat is manifested by increased antigen availability.

Jamaican fruit bats mount a stable and highly neutralizing antibody response after bat influenza virus infection.

Antibodies are an essential component of the antiviral response in many species, but to date, there is no compelling evidence that bats are capable of eliciting a robust humoral immunity, including neutralizing antibodies. Here, we report that infection of Jamaican fruit bats with the bat influenza A virus H18N11 elicits a rapid and stable humoral immune response with a strong neutralizing capacity, associated with no detectable viral shedding after repeat challenge infection. Thus, the neutralizing antibody response of bats might play an important role in the bat immunity.

Clinical immunogenicity outcomes from GENEr8-1, a phase 3 study of valoctocogene roxaparvovec, an AAV5-vectored gene therapy for hemophilia A.

Gene transfer therapies utilizing adeno-associated virus (AAV) vectors involve a complex drug design with multiple components that may impact immunogenicity. Valoctocogene roxaparvovec is an AAV serotype 5 (AAV5)-vectored gene therapy for the treatment of hemophilia A that encodes a B-domain-deleted human factor VIII (FVIII) protein controlled by a hepatocyte-selective promoter. Following previous results from the first-in-human phase 1/2 clinical trial, we assessed AAV5-capsid- and transgene-derived FVIII-specific immune responses with 2 years of follow-up data from GENEr8-1, a phase 3, single-arm, open-label study in 134 adult men with severe hemophilia A. No FVIII inhibitors were detected following administration of valoctocogene roxaparvovec. Immune responses were predominantly directed toward the AAV5 capsid, with all participants developing durable anti-AAV5 antibodies. Cellular immune responses specific for the AAV5 capsid were detected in most participants by interferon-γ enzyme-linked immunosorbent spot assay 2 weeks following dose administration and declined or reverted to negative over the first 52 weeks. These responses were weakly correlated with alanine aminotransferase elevations and showed no association with changes in FVIII activity. FVIII-specific cellular immune responses were less frequent and more sporadic compared with those specific for AAV5 and showed no association with safety or efficacy parameters.

Evaluation of comparative effect between aluminum hydroxide gel and montanide (ISA 70) in potency and protection of locally prepared rabbit hemorrhagic disease virus 2 (RHDV2) vaccines in rabbits.

BACKGROUND: Rabbit hemorrhagic disease (RHD) is an acute infectious disease that damages the rabbit industry by producing significant mortality rates in young and adult rabbits. RHD is better controlled by vaccination. OBJECTIVE: The current study's goal was to prepare and evaluate the immuno-enhancing effect of montanide ISA70 and aluminum hydroxide (Al(OH)3) gel incorporated within the inactivated RHDV2 vaccine and assess the vaccine's protective efficacy against the homologous and heterologous local RHDV2 strains in rabbits. METHODS: Inactivated RHDV vaccines were prepared using Montanide ISA70 oil or Al(OH)3 gel adjuvants and submitted to sterility, safety, and potency tests. 200 rabbits were equally divided into 4 groups: G1 (control), G2 (vaccinated with gel-incorporated vaccine), G3 (vaccinated with montanide-incorporated vaccine), and G4 (vaccinated with gel- and montanide-incorporated vaccines). Individual blood samples were collected from one week to six months from all groups. The vaccine's potency was measured by the HI test and protection percentage post challenge. RESULTS: Data revealed slightly increasing HI titer means reaching the 1st peak at 4 weeks post-vaccination (7.33, 7.67, and 7.33 log2 in the 2nd, 3rd, and 4th groups, respectively), then slightly decreasing and peaked again, giving 9.33 log2 for the2nd group at 3 months post-vaccination (MPV), 10.67 log2 for 3rd the group, and 10.33 log2 for the 4th group at 5 months post-vaccination. Titer gradually decreased but remained protective. The protection rate ranged from 80-100% and 80-90% for homologous and heterologous local RHDV2 vaccines, respectively, within 3 weeks and 6 months post-challenge. The montanide oil RHDV2 vaccine induced better protection than the aluminum gel RHDV2 vaccine. CONCLUSION: The results demonstrated evidence of cross-protection between RHDV2 strains. The oil emulsion vaccine induced higher and longer-lasting antibody titers than those obtained with the RHDV2 aluminum gel vaccine.

Antibody Isotype and Subclass Responses in Human Patients With Different Clinical Presentations of Sporotrichosis.

Sporotrichosis diagnosis involves a series of analyses, including culture and antibody detection in serum samples. Serologic methods may sometimes yield false-negative or false-positive results, leading to inaccurate diagnoses. This study assessed specific patient groups in which antibody detection of different isotypes and subclasses may lack sensitivity. An enzyme-linked immunosorbent assay (ELISA) with Sporothrix brasiliensis exoantigens was used to investigate IgM, IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgA1 and IgA2 antibodies in human serum samples. Eighty serum samples from patients with different sporotrichosis clinical manifestations, including cutaneous forms with and without hypersensitivity manifestations, extracutaneous forms (bone, ocular, meningeal and pulmonary), disseminated cutaneous forms and disseminated forms in individuals living with HIV/AIDS, diabetics and alcoholics, were evaluated. The ELISA sensitivities in the detection of different antibodies ranged from 0.85 to 0.60 for the detection of IgG2 and IgG3, respectively. The antibodies with higher area under ROC curves were IgG2, IgG, IgA and IgA1. There were no significant differences in the immunological reactivity of the tested antibodies among different clinical forms of sporotrichosis. The data revealed a higher likelihood of a false-negative outcome in patients with lesions in the nasal mucosa regarding the detection of IgM and a lower likelihood in patients with lymphocutaneous sporotrichosis regarding the detection of IgG3. Patients with hypersensitivity manifestations had a 3.71 odds ratio to yield negative results in total IgG detection. In conclusion, we identified specific patient groups in which antibody detection may lack sensitivity, thus contributing to a better understanding of the diagnostic challenges associated with this condition.

Evaluation the effect of dietary vitamin E, sesamin and thymoquinone bioactive compounds on immunological response, intestinal traits and MUC-2 gene expression in broiler Japanese quails (Coturnix japonica).

The current study was performed to determine the effect of dietary vitamin E, sesamin and thymoquinone bioactive lignans derived from sesame and black seed on immunological response, intestinal traits and Mucin2 gene expression in broiler quails. Three hundred and fifty (one days-old) quails were allotted to seven dietary treatments with five replicates as an experimental randomized design study. Treatments were basal diet as a control, control +100 and +200 mg of vitamin E, sesamin and thymoquinone per each kg of diet respectively. At 35 d of age, two quails from each pen were chosen, weighted, slaughtered, eviscerated and lymphoid organ relative weights were measured. Anti-body titers against Newcastle disease (ND), Sheep red blood cell (SRBC), and infectious bronchitis virus (IBV) and Avian influenza (AI) vaccination were determined. The serum activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum antioxidant activates such as superoxide dismutase (SOD),glutathione peroxidase(GPX), catalase (CAT) and total antioxidant capacity (TAC) were examined. The cell mediated immunity by dinitrochlorobenzene (DNCB) and phytohemagglutinin (PHA) challenges were assessed. The microflora populations of ileum, morphological traits of jejunum and mucin2 gene expression were analyzed. Data showed that the lymphoid organ (thymus, spleen and Bursa) relative weights and antibody titer against HI, AI, SRBC and IB vaccination were increased compared to the control (p ≤ 0.05). Serum activities of ALP, ALT and AST were decreased under influences of dietary treatments (p ≤ 0.05). The serum antioxidant activates of GPX,SOD,CAT and TAC were increased and Increasing in mean skin thickness after DNCB challenge and decrease wing web swelling response to PHA mitojen injection were observed (p ≤ 0.05). Salmonella enterica, E-coli and Coliforms colonies were decrease and Lactobacillus colonies increased instead (p ≤ 0.05). The villus height and surface, crypt depth and goblet cells density were increased compared to the control (p ≤ 0.05). The expression of MUC2 gene increased under influnces of vitamin E, sesamin and thymoquinone supplemented diets (p ≤ 0.05).

Severity of papular urticaria in children is associated with specific IgG4 anti-salivary gland antigens from Aedes aegypti.

Summary: Background. Papular Urticaria (PU) is a cutaneous hypersensitivity disorder triggered by hematophagous arthropod bites. Despite being a common condition, especially in tropical environments, many knowledge gaps are observed for this disease. The main objective of this study was to investigate the patterns of humoral immune response to mosquito antigens in children with PU and establish a correlation between this response and the severity of clinical symptoms. Methods. An analytical cross-sectional observational study was carried out. Clinical and sociodemographic data and children's blood samples were collected to measure the specific antibodies from: 1. A. aegypti salivary gland antigens; 2. A. aegypti whole body antigens (both produced in the laboratory of the Center for Health Sciences at the Federal University of Rio de Janeiro). A PU severity score based on clinical data is proposed to correlate disease severity with antibody reactivity signatures. Results. According to the clinical data, 58.9% of children received high severity scores. A significant statistical correlation was found between patients with high PU severity score and the development of symptoms before the age of two (p = 0.0326) and high IgG4 anti-salivary gland antigens concentration (p less than 0.05). Conclusion. It is suggested that PU severity in children is associated with a high concentration of IgG4 anti-salivary gland antigens from Aedes aegypti. Further studies are recommended to deepen the understanding of the mechanisms involved.

The Structural Characterization of a Polysaccharide from the Dried Root of Salvia miltiorrhiza and Its Use as a Vaccine Adjuvant to Induce Humoral and Cellular Immune Responses.

In order to supplement the research gap concerning Salvia miltiorrhiza polysaccharide extracted from Danshen in NMR analysis, and to clarify its immune enhancement effect as an adjuvant, we isolated and purified SMPD-2, which is composed of nine monosaccharides such as Ara, Gal, and Glc from Danshen. Its weight average molecular weight was 37.30 ± 0.096 KDa. The main chain was mainly composed of →4)-α-D-Galp-(1→, →3,6)-ß-D-Glcp-(1→ and a small amount of α-L-Araf-(1→. After the subcutaneous injection of SMPD-2 as an adjuvant to OVA in mice, we found that it enhanced the immune response by activating DCs from lymph nodes, increasing OVA-specific antibody secretion, stimulating spleen lymphocyte activation, and showing good biosafety. In conclusion, SMPD-2 could be a promising candidate for an adjuvant.

Antibodies to oral pathobionts and colon cancer risk in the CLUE I cohort study.

Periodontitis has been associated with an increased risk for gastrointestinal cancers. The objective of our study was to investigate the association of antibodies to oral bacteria and the risk of colon cancer in a cohort setting. Using the CLUE I cohort, a prospective cohort initiated in 1974 in Washington County, Maryland, we conducted a nested case-control study to examine the association of levels of IgG antibodies to 11 oral bacterial species (13 total strains) with risk of colon cancer diagnosed a median of 16 years later (range: 1-26 years). Antibody response was measured using checkerboard immunoblotting assays. We included 200 colon cancer cases and 200 controls matched on age, sex, cigarette smoking status, time of blood draw and pipe or cigar smoking status. Controls were selected using incidence density sampling. Conditional logistic regression models were used to assess the association between antibody levels and colon cancer risk. In the overall analysis, we observed significant inverse associations for 6 of the 13 antibodies measured (P-trends <.05) and one positive association for antibody levels to Aggregatibacter actinomycetemcomitans (ATCC 29523; P-trend = .04). While we cannot rule out a role for periodontal disease in colon cancer risk, findings from our study suggest that a strong adaptive immune response may be associated with a lower risk of colon cancer. More studies will need to examine whether the positive associations we observed with antibodies to A. actinomycetemcomitans reflect a true causal association for this bacterium.

Interleukin-9 rescues class switching of Memory B cells derived from Common variable immunodeficiency patients.

Impaired class switch memory (CSM) B cell formation is the hallmark of common variable immunodeficiency (CVID). Various T cell abnormalities have been observed in CVID patients indicating inadequate T-cell help to B cells. A major setback in understanding its pathogenesis is due to diverse clinical presentation. Therefore, we performed extensive immunological investigation in a cohort of CVID patients with similar clinical findings in order to unravel the T cell dysfunction and its influence on the defective humoral immune response. All recruited CVID patients exhibited B cells in the normal range, but reduced CSM B cells. However, patients showed reduced T cell proliferation, reduced level of serum Interleukin-9 (IL-9) and frequency of IL-9 expressing CD4 (Th-9) cells. IL-9 supplementation along with CD40 engagement was effective in inducing in vitro CSM B cells formation in CVID patients. Thus, IL-9 supplementation has the potential to restore impaired CSM B cell formation in CVID.

Consistent neutralization of circulating omicron sub-variants by hybrid immunity up to 6 months after booster vaccination.

The current COVID-19 vaccination program requires frequent booster vaccination to maintain sufficient neutralization levels against immune evasive SARS-CoV-2 variants. However, prior studies found more potent and durable immune response in convalescing individuals, raising the possibility of less frequent booster vaccination for them. Here, we conducted a longitudinal immunological study based on two prospective cohorts of booster vaccinated convalescing COVID-19 patients or healthcare workers (HCW) without COVID-19 history in Xiangyang, China. Comparing to 1-month post-boosting, pseudovirus neutralization titers (pVNT50) of ancestral Wuhan-Hu-1 and circulating omicron sub-variants BA.5, BF.7, BA.4.6, BA.2.75, and BA.2.75.2 spikes were stable or even increased in convalescing samples at 6-month post-boosting, when HCW samples showed substantial drop of neutralization titers across the spectrum. Variant-to-Wuhan-Hu-1 pVNT50 ratios showed no significant variation during the 17 months from pre-vaccination to 6-month post-boosting in convalescing individuals, indicating that the high durability of hybrid immunity was likely sustained by continuously improving neutralization potency that compensated immune decay. Our data provide mechanistic insight into prior epidemiological findings that vaccine-elicited humoral immune response was more durable in convalescing individuals than those without SARS-CoV-2 infection, and suggest further research into potential extension of boosting intervals for convalescing individuals.

A hepatitis B virus core antigen-based virus-like particle vaccine expressing SARS-CoV-2 B and T cell epitopes induces epitope-specific humoral and cell-mediated immune responses but confers limited protection against SARS-CoV-2 infection.

The hepatitis B virus core antigen (HBcAg) tolerates insertion of foreign epitopes and maintains its ability to self-assemble into virus-like particles (VLPs). We constructed a ∆HBcAg-based VLP vaccine expressing three predicted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B and T cell epitopes and determined its immunogenicity and protective efficacy. The recombinant ∆HBcAg-SARS-CoV-2 protein was expressed in Escherichia coli, purified, and shown to form VLPs. K18-hACE2 transgenic C57BL/6 mice were immunized intramuscularly with ∆HBcAg VLP control (n = 15) or ∆HBcAg-SARS-CoV-2 VLP vaccine (n = 15). One week after the 2nd booster and before virus challenge, five ∆HBcAg-SARS-CoV-2 vaccinated mice were euthanized to evaluate epitope-specific immune responses. There is a statistically significant increase in epitope-specific Immunoglobulin G (IgG) response, and statistically higher interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) expression levels in ∆HBcAg-SARS-CoV-2 VLP-vaccinated mice compared to ∆HBcAg VLP controls. While not statistically significant, the ∆HBcAg-SARS-CoV-2 VLP mice had numerically more memory CD8+ T-cells, and 3/5 mice also had numerically higher levels of interferon gamma (IFN-γ) and tumor necrosis factor (TNF). After challenge with SARS-CoV-2, ∆HBcAg-SARS-CoV-2 immunized mice had numerically lower viral RNA loads in the lung, and slightly higher survival, but the differences are not statistically significant. These results indicate that the ∆HBcAg-SARS-CoV-2 VLP vaccine elicits epitope-specific humoral and cell-mediated immune responses but they were insufficient against SARS-CoV-2 infection.

Cross-reactive immune responses to monkeypox virus induced by MVA vaccination in mice.

Mpox (monkeypox) infection cases increased recently in non-Mpox outbreak areas, potentially causing an international threat. The desire to defend against a potential outbreak has led to renewed efforts to develop Mpox vaccines. In this report, mice were immunized with various doses of modified vaccinia virus Ankara (MVA) to evaluate the cross-reactive immune response of MVA immunization against protective antigens of the current monkeypox virus. We demonstrated that MVA induced specific antibodies against protective antigens (A29, A35, B6, M1, H3, and I1), mediating the neutralization abilities against the MVA and the monkeypox virus (MPXV). Moreover, recombinant protective antigens of the MPXV elicited cross-binding and cross-neutralizing activities for MVA. Hence, the MVA induced cross-reactive immune responses, which may guide future efforts to develop vaccines against the recent MPXV. Notably, compared to the other protective antigens, the predominant A29 and M1 antigens mediated higher cross-neutralizing immune responses against the MVA, which could serve as antigen targets for novel orthologous orthopoxvirus vaccine.

COVID-19 booster dose induces robust antibody response in pregnant, lactating, and nonpregnant women.

BACKGROUND: Although emerging data during the SARS-CoV-2 pandemic have demonstrated robust messenger RNA vaccine-induced immunogenicity across populations, including pregnant and lactating individuals, the rapid waning of vaccine-induced immunity and the emergence of variants of concern motivated the use of messenger RNA vaccine booster doses. Whether all populations, including pregnant and lactating individuals, will mount a comparable response to a booster dose is not known. OBJECTIVE: This study aimed to profile the humoral immune response to a COVID-19 messenger RNA booster dose in a cohort of pregnant, lactating, and nonpregnant age-matched women. STUDY DESIGN: This study characterized the antibody response against ancestral Spike and Omicron in a cohort of 31 pregnant, 12 lactating, and 20 nonpregnant age-matched controls who received a BNT162b2 or messenger RNA-1273 booster dose after primary COVID-19 vaccination. In addition, this study examined the vaccine-induced antibody profiles of 15 maternal-to-cord dyads at delivery. RESULTS: Receiving a booster dose during pregnancy resulted in increased immunoglobulin G1 levels against Omicron Spike (postprimary vaccination vs postbooster dose; P=.03). Pregnant and lactating individuals exhibited equivalent Spike-specific total immunoglobulin G1, immunoglobulin M, and immunoglobulin A levels and neutralizing titers against Omicron compared with nonpregnant women. Subtle differences in Fc receptor binding and antibody subclass profiles were observed in the immune response to a booster dose in pregnant vs nonpregnant individuals. The analysis of maternal and cord antibody profiles at delivery demonstrated equivalent total Spike-specific immunoglobulin G1 in maternal and cord blood, yet higher Spike-specific FcγR3a-binding antibodies in the cord relative to maternal blood (P=.002), consistent with the preferential transfer of highly functional immunoglobulin. Spike-specific immunoglobulin G1 levels in the cord were positively correlated with the time elapsed since receiving the booster dose (Spearman R, .574; P=.035). CONCLUSION: Study data suggested that receiving a booster dose during pregnancy induces a robust Spike-specific humoral immune response, including against Omicron. If boosting occurs in the third trimester of pregnancy, higher Spike-specific cord immunoglobulin G1 levels are achieved with greater time elapsed between receiving the booster and delivery. Receiving a booster dose has the potential to augment maternal and neonatal immunity.

Humoral and cellular immune responses after three or four doses of BNT162b2 in patients with hematological malignancies.

OBJECTIVES: Initial responses to coronavirus disease 2019 vaccination are impaired in patients with hematological malignancies. We investigated immune responses after three or four doses of BNT162b2 in patients with myeloid and lymphoid malignancies compared to controls, and identified risk factors for humoral and cellular nonresponse 1 year after first vaccination. METHODS: In 407 hematological patients (45 myeloid, 362 lymphoid) and 98 matched controls, we measured immunoglobulin G (IgG) and neutralizing antibodies specific for the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline, 3 weeks, 2, 6, and 12 months, and interferon-γ release at 12 months. RESULTS: In patients with lymphoid malignancies, SARS-CoV-2 receptor-binding domain IgG concentration and mean neutralizing capacity was lower than in controls at all time points. A diagnosis of chronic lymphocytic B-cell leukemia (CLL) or lymphoma was associated with humoral nonresponse at 12 months compared to having multiple myeloma/amyloidosis (p < .001 and p = .013). Compared to controls, patients with lymphoid malignancies had increased risk of cellular nonresponse. A lymphoma diagnosis was associated with lower risk of cellular nonresponse compared to patients with multiple myeloma/amyloidosis, while patients with CLL had comparable response rates to patients with multiple myeloma/amyloidosis (p = .037 and p = .280). CONCLUSIONS: In conclusion, long-term humoral and cellular immune responses to BNT162b2 were impaired in patients with lymphoid malignancies.

Kinetics of COVID-19 mRNA primary and booster vaccine-associated neutralizing activity against SARS-CoV-2 variants of concern in long-term care facility residents: a prospective longitudinal study in Japan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) remains a threat to vulnerable populations such as long-term care facility (LTCF) residents, who are often older, severely frail, and have multiple comorbidities. Although associations have been investigated between COVID-19 mRNA vaccine immunogenicity, durability, and response to booster vaccination and chronological age, data on the association of clinical factors such as performance status, nutritional status, and underlying comorbidities other than chronological age are limited. Here, we evaluated the anti-spike IgG level and neutralizing activity against the wild-type virus and Delta and Omicron variants in the sera of LTCF residents, outpatients, and healthcare workers before the primary vaccination; at 8, 12, and 24 weeks after the primary vaccination; and approximately 3 months after the booster vaccination. This 48-week prospective longitudinal study was registered in the UMIN Clinical Trials Registry (Trial ID: UMIN000043558). RESULTS: Of 114 infection-naïve participants (64 LTCF residents, 29 outpatients, and 21 healthcare workers), LTCF residents had substantially lower anti-spike IgG levels and neutralizing activity against the wild-type virus and Delta variant than outpatients and healthcare workers over 24 weeks after the primary vaccination. In LTCF residents, booster vaccination elicited neutralizing activity against the wild-type virus and Delta variant comparable to that in outpatients, whereas neutralizing activity against the Omicron variant was comparable to that in outpatients and healthcare workers. Multiple regression analyses showed that age was negatively correlated with anti-spike IgG levels and neutralizing activity against the wild-type virus and Delta variant after the primary vaccination. However, multivariate regression analysis revealed that poor performance status and hypoalbuminemia were more strongly associated with a lower humoral immune response than age, number of comorbidities, or sex after primary vaccination. Booster vaccination counteracted the negative effects of poor performance status and hypoalbuminemia on the humoral immune response. CONCLUSIONS: LTCF residents exhibited suboptimal immune responses following primary vaccination. Although older age is significantly associated with a lower humoral immune response, poor performance status and hypoalbuminemia are more strongly associated with a lower humoral immune response after primary vaccination. Thus, booster vaccination is beneficial for older adults, especially those with a poor performance status and hypoalbuminemia.

Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting.

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (≤ or ≥60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants - ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post-omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months.

Construction, Expression, and Evaluation of the Naturally Acquired Humoral Immune Response against Plasmodium vivax RMC-1, a Multistage Chimeric Protein.

The PvCelTOS, PvCyRPA, and Pvs25 proteins play important roles during the three stages of the P. vivax lifecycle. In this study, we designed and expressed a P. vivax recombinant modular chimeric protein (PvRMC-1) composed of the main antigenic regions of these vaccine candidates. After structure modelling by prediction, the chimeric protein was expressed, and the antigenicity was assessed by IgM and IgG (total and subclass) ELISA in 301 naturally exposed individuals from the Brazilian Amazon. The recombinant protein was recognized by IgG (54%) and IgM (40%) antibodies in the studied individuals, confirming the natural immunogenicity of the epitopes that composed PvRMC-1 as its maintenance in the chimeric structure. Among responders, a predominant cytophilic response mediated by IgG1 (70%) and IgG3 (69%) was observed. IgM levels were inversely correlated with age and time of residence in endemic areas (p < 0.01). By contrast, the IgG and IgM reactivity indexes were positively correlated with each other, and both were inversely correlated with the time of the last malaria episode. Conclusions: The study demonstrates that PvRMC-1 was successfully expressed and targeted by natural antibodies, providing important insights into the construction of a multistage chimeric recombinant protein and the use of naturally acquired antibodies to validate the construction.

Humoral response to SARS-CoV-2 and seasonal coronaviruses in COVID-19 patients.

We used enzyme-linked immunoassay methods to measure the prevalence and the levels of antibody responses to the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and four seasonal human coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV 229E, and HCoV-NL63) in a cohort of 115 convalescent plasma donors infected with SARS-CoV-2 (1-61 days after symptom onset) compared to antibody levels in 114 individuals with no evidence of a recent infection with SARS-CoV-2. In the humoral response to the four seasonal coronaviruses, only HCoV-HKU1- and HCoV-229E-assays showed slightly elevated antibody levels in the COVID group compared to the control group. While in the COVID-group the levels of SARS-CoV-2 antibodies correlated significantly with disease severity, no association was found in the levels of antibodies against the seasonal coronaviruses. The most striking result in both groups was that the levels of antibodies against all tested coronaviruses, including the new SARS-CoV-2 showed a highly significant correlation with each other. There seems to be an individual predisposition to a weaker or stronger humoral immune response against all known seasonal human coronaviruses including the new SARS-CoV-2, which could lead to a definition of low and high responders against human coronaviruses with potential impact on the assessment of postinfection antibody levels and protection.