IgG Ratio Research Articles

Effect of HIV and Malaria in Pregnancy on Pertussis-specific Antibodies and Transplacental Antibody Transfer: A Secondary Analysis of a Prospective Cohort Study in Mozambican Pregnant Women and Their Infants.

Infection during pregnancy may affect maternal and infant immunity against childhood diseases. We aimed to evaluate the effects of maternal HIV and malaria on maternal and infant pertussis immunity and placental antibody transfer. A prospective study was conducted in mother-infant pairs in Mozambique. Peripheral and cord blood samples were collected for pertussis-specific immune assays. Maternal HIV serostatus and Plasmodium falciparum infection were assessed. The placental transfer was assessed using cord-to-mother ratios of IgG against pertussis toxin (PT), pertactin (PRN) and fimbriae 2/3 (FIM). A total of 270 mother-infant pairs were included: 99 mothers with HIV and 40 mothers with malaria. Pregnant women with HIV showed a reduction in placental transfer [PT: 12.7%, 95% confidence interval (CI): 2.6-21.7, P = 0.015; PRN: 14.6%, 95% CI: 6.3-22.1, P = 0.001; and FIM: 7.5%, 95% CI: -6.6 to 19.7, P = 0.282] compared with women without HIV. A trend toward reduction in IgG transfer was observed among women with malaria (PT: 9.5%, 95% CI: -4.2 to 21.4, P = 0.165; PRN: 5.0%, 95% CI: -7.0 to 15.7, P = 0.394; and FIM: 15.9%, 95% CI: -0.9 to 30.0, P = 0.062) compared with those without. Maternal HIV infection (odds ratio: 4.43, 95% CI: 2.14-9.1; P < 0.001) and high viral load (odds ratio: 4.37, 95% CI: 1.4-12.2; P = 0.033) were associated with impaired placental transfer. Maternal HIV infection is associated with lower mother-to-infant transfer of pertussis antibodies. While efforts continue in the health care of pregnant women with HIV, interventions such as maternal immunization can be a valuable strategy to prevent pertussis in infants.

Prediction of long-term outcomes in patients with chronic hepatitis D infection by quantitative HBcrAg/anti-HBc IgG ratio

Prediction of long-term outcomes in patients with chronic hepatitis D infection by quantitative HBcrAg/anti-HBc IgG ratio

Perinephric myxoid pseudotumor of fat: A series of 13 cases and literature review

Perinephric myxoid pseudotumor of fat (PMPF) is a recently described and rare retroperitoneal mass-forming lesion whose clinical significance chiefly involves mimicry of a variety of soft tissue tumors. For unknown reasons, it commonly occurs in male patients with underlying non-neoplastic renal diseases and/or type 2 diabetes (DMT2). A total of 55 cases have been reported in the literature. Recently, we have encountered 13 such masses with peculiar histologic features; thus, we sought to investigate our experience and review the clinicopathologic characteristics of the literature. Our series confirms that PMPF frequently occurs in adult male patients (11/13, 85%), with an average age of 66 years, and commonly co-occurs with renal disease, such as DMT2 (2/13, 15%), end-stage renal disease (ESRD) (5/13, 39%), renal cysts (4/13, 31%), concurrent or prior renal neoplasia (2/13; 15%), and myeloma/lymphoma (2/13; 15%). Histologic evaluation shows lipomatous masses commonly showing variable amounts of fat necrosis, myxoid degeneration, lymphoplasmacytic inflammation and lacking atypical hyperchromatic stromal spindle cells. Unusual histologic features include extramedullary hematopoiesis (1/13, 8%), hemosiderin deposition (4/13, 31%), and small wisps of mature smooth muscle (6/13, 46%). All cases tested were negative for MDM2 and did not show an increased ratio of IgG4+/IgG+ plasma cells. Our study confirms the clinical and pathologic features of PMPF and expands its histologic spectrum, underscoring the importance of this entity as a benign pseudotumor which should be included in the differential diagnosis of other fat-containing retroperitoneal masses, particularly well-differentiated liposarcoma.

Aortic Valve Replacement Surgery Caused by IgG4-Related Aortic Regurgitation

While IgG4-related disease affects different organs, it is uncommon to associate it with the aortic valve. The clinical manifestations and prognosis of an uncommon IgG4-related aortic valve disease were examined by reporting it. After common activity, a 50-year-old man experienced shortness of breath and chest tightness. IgG4+ was expressed at a level of 4.23 g/L. The aortic valve had severe reflux, and the ascending aorta and aortic sinus were dilated, as evidenced by transesophageal echocardiography. Pathological results suggested that the ratio of IgG4+ cells to IgG+ cells was over 40%. Thus, the patient was diagnosed with aortic valve disease caused by IgG4+. Surgical treatment was executed. In clinical practice, IgG4-associated aortic regurgitation is uncommon and has the same clinical manifestations as general aortic valve disease. Nevertheless, there was a significant increase in serum IgG4+ levels. There was an association between the two. The pathology of valves can be proven.

Role of IgM/ IgG Ratio in Distinguishing Primary and Secondary Dengue Viral Infections: A Cross-Sectional Study.

Objectives In recent years, Uttarakhand, a state in North India has become one of the prime spots for tourism all over the world. Thereby, a tremendous increase in the epidemics of dengue infection has been observed recently. Secondary dengue causes more severe disease in comparison with primary, thus to differentiate the two is very crucial. We aim to find out the cut-off values of the IgM:IgG ratio for early detection of secondary dengue which could further help clinicians to prevent the complications. Methods A cross-sectional study was conducted over one year involving around 936 suspected cases of dengue. Samples were tested using the commercially available capture enzyme linked Immunosorbent assay (ELISA) method for IgM and IgG. Real-time and nested polymerase chain reaction (PCR) tests were also done to find out the prevalent serotype. IgM:IgG ratio was evaluated by using receiver operating characteristic curve analysis for the differentiation of primary and secondary dengue. Results Among the total 91 serologically confirmed dengue patients, forty-seven (51.6%) were found to be primary, and forty-four (48.4%) were secondary dengue infections with male preponderance. Using the WHO diagnostic criteria, patients with dengue fever (DF) without warning signs added up to 51.6%, with warning signs 42.9% and severe dengue 5.5% of the total cases. The cut-off ratio of IgM:IgG ratio = 1.59 found the best discrimination between primary and secondary infection. Forty out of ninety-one (44%) patients exhibited ratios of > 1.59 whereas the rest fifty-one (56%) exhibited ratios of < 1.59. Dengue virus - 2 (DENV- 2) was found to be the most prevalent serotype. Conclusion Our study recommends the cut-off values for IgM:IgG ratio as 1.59. Therefore it is hoped that this will guide the clinicians to early distinguish between primary and secondary dengue. Furthermore, it can reduce morbidity and mortality because of dengue infections in the future.

Serodiagnosis of Secondary Dengue Infection in a Tertiary Care Hospital, Mysuru

Dengue is one among the acute viral infections with the probability of fatal complications. In 2017; NVBDCP reported 157220 positive dengue cases with 250 deaths in India; 17018 cases and 5 deaths in Karnataka. Most primary infections are uneventful. The critical illness like Dengue Haemorrhagic Fever and Dengue Shock Syndrome are generally attributed to serotype cross-reactivity. Identification of secondary dengue infection in the early onset of illness is beneficial. Therefore, methods to discrepate primary and secondary dengue infection are of significant prognostic value. The current study is a hospital based prospective analytical evaluation and was aimed to discriminate secondary from primary dengue virus infection in clinically suspected dengue cases presenting with fever and thrombocytopenia. Patients of all age groups attending Krishna Rajendra Hospital on outpatient and inpatient basis with clinically suspected dengue fever of less than 5 days associated with thrombocytopenia were included in the study. The samples were tested in the VRDL of the Microbiology Department for dengue NS1 antigen and IgM antibodies, positive for both were further subjected to IgG antibodies. IgM /IgG ratio was used to differentiate primary and secondary dengue infections. Dengue infection was categorized based on WHO guidelines. A total of 17,841 samples were tested from May 2017 to December 2023; out of 17841 samples tested 2111 (60.74%) were positive for dengue NS1 and IgM. Of the 2111 dengue NS1 and IgM positive cases, 1700 (80.5%) were having secondary dengue infection, whereas 411 (19.46%) were having primary infection. Early detection of secondary infection helps the clinician in anticipating dengue related complications with appropriate therapeutic intervention, thereby reducing further complications and mortality.

Efficacy of rituximab in treating steroid-resistant Graves’ orbitopathy in active moderate-to-severe and sight-threatening forms: A retrospective observation from China

Background and objectivesThe efficacy of rituximab (RTX) in treating steroid-resistant Graves’ orbitopathy (GO) has been limitedly studied in Asians. Moreover, RTX has been considered even less for patients with steroid-resistant dysthyroid optic neuropathy (DON) who failed to undergo orbital decompression surgery for physical or financial reasons, or who responded poorly to the procedure. This study aimed to investigate the efficacy of RTX in treating steroid-resistant active moderate-to-severe and sight-threatening GO in a Chinese population. MethodsData from 28 patients with steroid-resistant GO prescribed a single dose of 500 mg RTX were retrospectively retrieved. Treatment responses and contributing factors were analyzed. ResultsThe median follow-up time was 22 (8–34) weeks. 23 (82.1 %) patients had a positive objective outcome recommended by the European Group on Graves’ Orbitopathy (EUGOGO), while 25 (92.6 %) had a decrease in 7-item clinical activity score (CAS) by at least 2. Diplopia, visual dysfunction, and MRI-detected T2 relaxation time of the involved extraocular muscles improved significantly at the last follow-up compared to baseline (81.0 % vs. 47.6 %, 38.9 % vs. 16.7 %, and 87.8 (8.64) vs. 75.8 (10.9) ms, respectively; all p values < 0.05). No significant improvement was seen in terms of proptosis and eye muscle duction. Notably, a higher baseline IgG4 to IgG ratio was a predictor for RTX-induced positive EUGOGO outcomes. After RTX treatment, all 8 patients with DON demonstrated inactivation, and 4 improved in visual acuity by ≥ 1 line. No patient with DON experienced obvious deterioration. ConclusionA single dose of 500 mg RTX seemed to be an effective and tolerable treatment for steroid-resistant GO. However, larger-scale studies with a control group are required for a more solid conclusion. The role of RTX in steroid-resistant DON management where surgery is unavailable or ineffective should be further explored.

Evaluation of antibody responses in healthy individuals receiving SARS-CoV-2 inactivated vaccines

Inactivated coronavirus disease 2019 (COVID-19) vaccines such as CoronaVac and BBIBP-CorV have been widely used in China. However, more investigation is still needed to understand antibodies' duration and effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the real world. In this study, 575 participants who had been vaccinated with two or three doses of the inactivated vaccine were recruited. Serum samples were collected and tested for anti-spike IgG and neutralizing antibodies against SARS-CoV-2 (original strain, Dela, and Omicron). Unsurprisingly, a third dose of the vaccine significantly enhanced antibody responses against SARS-CoV-2 and its variants. However, despite a booster dose, the neutralizing antibody levels against Omicron, particularly the BA.5.2 subvariant, remained low. There was no sex bias, but an age bias was observed. Notably, the predominant IgG subclass antibodies were IgG1 and IgG2, with a much lower level of IgG4. After the booster shot, the ratio of IgG4 to IgG1 significantly increased. The observation of IgG1 to the IgG4 class switch after repeated inactivated vaccinations underscores the importance of continuous monitoring of subclass antibody responses. Further clinical investigations are required to understand the implications of this class switch for optimizing immunization strategies.

Imbalance of Tfollicular helper cell subsets trigger the differentiation of pathogenic B cells in idiopathic membranous nephropathy.

This study aims to elucidate the role of T follicular helper (Tfh) cells and their subsets in idiopathic membranous nephropathy (IMN). The frequencies of Tfh cell subsets and B cell subsets in peripheral blood (PB) were detected in both IMN patients and healthy controls (HCs). The involvement of Tfh cells in the disease pathogenesis was examined by coculturing human Tfh cells with B cells. The dynamic changes of Tfh cells in PB or spleen were monitored in passive Heymann nephritis (PHN) rats. The frequencies of circulating Tfh (cTfh) cells, cTfh2 cells, and plasmablasts were enriched in the PB of patients with IMN. cTfh cells expressed higher ICOS, and lower BTLA than healthy counterparts. The frequency of ICOS + cTfh2 was associated with the severity of IMN, including 24h urine protein, IgG4 concentration and the IgG4: IgG ratio. Positive correlations were also observed between the frequency of cTfh2 cells with plasmablasts, serum IL-21 and IL-4 levels. Importantly, cTfh cells isolated from IMN patients were able to induce the differentiation of B cells to memory B cells (MBC) and plasmablasts, this process could be substantially attenuated by blocking the IL-21. Similar increases of ICOS + cTfh cells were also detected in spleen of PHN rats, concomitant with elevated urine protein levels. Collectively, our results demonstrate that the imbalance of cTfh cell subsets play a crucial pathogenic role in IMN by inducing the differentiation of B cells through IL-21, and cTfh2 cells might serve as useful markers to evaluate the progression of IMN.

Immunogenicity at delivery after Tdap vaccination in successive pregnancies.

Tetanus, diphtheria, acellular pertussis (Tdap) vaccination is recommended to be administered in every pregnancy. Although the safety of this strategy has been confirmed, the immunogenicity of Tdap vaccination in two successive pregnancies has not yet been described. This study investigated Tdap-specific immunity levels and transplacental transfer in two successive pregnancies after repeated Tdap-vaccination. Women enrolled in prior studies on Tdap vaccination during pregnancy were invited to participate in a follow-up study if they became pregnant again. Women who received a Tdap vaccine in both pregnancies were considered for this analysis. Tdap-specific total IgG and IgG subclasses were measured with a multiplex immunoassay. In total, 27 participants with a mean interval between deliveries of 2.4 years were included in the analysis. In maternal serum, Tdap-specific total IgG levels were comparable at both deliveries whereas in cord serum, all Tdap-specific total IgG antibody levels were reduced at the second compared to the first delivery. This was largely reflected in the IgG1 levels in maternal and cord serum. Transplacental transfer ratios of total IgG and IgG1 were also mostly reduced in the second compared to the first pregnancy. This study reports for the first time Tdap-specific total IgG and IgG subclass levels and transfer ratios after repeated Tdap vaccination in successive pregnancies. We found reduced transfer of most Tdap-specific IgG and IgG1 antibodies in the successive pregnancy. As pertussis-specific antibodies wane quickly, Tdap vaccination in each pregnancy remains beneficial. However, more research is needed to understand the impact of closely spaced booster doses during pregnancy on early infant protection against pertussis.

Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.

479. Optimizing maternal COVID-19 vaccine antibodies in low birthweight infants: is timing everything?

Abstract Background COVID-19 vaccines in pregnancy may protect young infants from severe illness via maternally-derived IgG. Transplacental transfer of maternal IgG is thought to be decreased in infants with low-birth weight (LBW). The impact of maternal COVID-19 vaccine in this population is unknown. We aimed to evaluate anti-Spike (S) IgG transfer in LBW versus normal birthweight (NBW) infants. Methods In this prospective cohort study among individuals with a singleton pregnancy without detectable anti-nucleocapsid IgG who received at least 2 doses of an mRNA COVID-19 vaccine prior to delivery, we tested paired maternal and cord samples for anti-S IgG. We used linear regression to evaluate associations between LBW (birthweight &amp;lt; 2500 grams), timing of vaccine dose, and anti-S IgG. We included as covariates timing of last vaccine dose, gestational age at delivery, number of doses prior to delivery, and small for gestational age (&amp;lt; 10th percentile) birthweight. Results We tested maternal/cord anti-S IgG from 33 LBW and 203 NBW pregnancies. The median gestational age at delivery and birthweight was 34.7 weeks/1925 grams for LBW infants compared to 39.4 weeks/3375 grams for NBW infants. Median maternal anti-S IgG was 6128 BAU/mL (IQR:2223,11722) and 1260 BAU/mL (IQR:519,7307) for LBW and NBW infants, respectively. Median cord anti-S IgG was 4585 BAU/mL (IQR:2124,12721) and 1734 BAU/mL (IQR:876, 8812) for LBW and NBW infants, respectively (Figure 1). After adjustment for covariates including vaccine dose timing, there was no difference between cord anti-S IgG concentrations of LBW and NBW infants (beta: -0.01; 95% confidence interval [CI]: -0.68,0.65; p=0.97). As time between last dose and delivery increased, cord anti-S IgG concentrations significantly decreased (beta: -0.0.03; 95% CI: -0.05,-0.02; p &amp;lt; 0.01; Figure 2b). In contrast, cord:maternal IgG ratios significantly increased with greater time between last vaccine dose and delivery (beta: 0.01; 95% CI: 0.01,0.02; p&amp;lt; 0.01; Figure 3). Figure 3 Conclusion Maternal IgG levels may be more important predictors than infant birthweight for SARS-CoV-2 cord IgG concentrations. Policy regarding timing of COVID-19 vaccine during pregnancy should consider pregnancies at risk for LBW infants. Disclosures Alisa B. Kachikis, MD, MSc, Merck: Grant/Research Support|Pfizer: Grant/Research Support Mindy Pike, PhD, Merck: Grant/Research Support Alexander L. Greninger, MD, PhD, Cepheid: central contracts|Hologic: central contracts|Janssen: central contracts|Novavax: central contracts|Pfizer: central contracts Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant

478. COVID-19 maternal antibody concentrations in twin infants: impact of multiple pregnancy on transplacental antibody transfer during pregnancy

Abstract Background COVID-19 vaccines in pregnancy protect both pregnant individuals and young infants from severe illness via transplacental transfer of maternally-derived IgG. However, the impact of multiple (e.g. twin) pregnancy on transplacental transfer of SARS-CoV-2 IgG is unknown. We aimed to evaluate anti-Spike (S) antibody transfer among infants from twin pregnancies compared to singleton pregnancies. Methods We conducted a prospective cohort study among individuals with twin and singleton pregnancies who received at least 2 doses of an mRNA COVID-19 vaccine prior to delivery. We tested paired maternal and cord samples for anti-S IgG and used linear regression to evaluate associations between multiple or singleton pregnancy and anti-S antibody. We included as covariates timing of last vaccine dose, gestational age at delivery, number of doses prior to delivery, and small for gestational age (&amp;lt; 10th percentile) birthweight. Results We tested maternal/cord anti-S IgG from 25 twin and 291 singleton pregnancies. The median gestational age at delivery was 36 weeks for twin infants compared to 39 weeks for singleton infants. Median maternal anti-S IgG was 5812 BAU/mL (IQR:754, 16061) and 2971 BAU/mL (IQR:706, 14000) for twin and singleton pregnancies, respectively. Median cord anti-S IgG was 4110 BAU/mL (IQR: 527, 15937) and 3636 BAU/mL (IQR: 1019, 15465) for twin and singleton infants, respectively (Figure 1). Cord:maternal IgG ratios were significantly lower in twin pregnancies compared to singleton pregnancies (p &amp;lt; 0.01; Figure 2). After adjustment for covariates, there was no difference between maternal anti-S IgG concentrations (beta: -0.54; 95% confidence interval [CI]: -1.26,0.18; p=0.14), cord anti-S IgG concentrations (beta: -0.77; 95% CI: -1.68,0.13; p=0.10) or cord:maternal IgG ratios (beta: -0.07; 95% CI: -0.32,0.19; p=0.61) between twin and singleton pregnancies. Conclusion Twin and singleton infants benefit similarly from maternal COVID-19 vaccine during pregnancy. Higher risk pregnancies including multiple pregnancies should be considered in health policy discussions regarding COVID-19 vaccine timing in pregnancy. Disclosures Alisa B. Kachikis, MD, MSc, Merck: Grant/Research Support|Pfizer: Grant/Research Support Mindy Pike, PhD, Merck: Grant/Research Support Alexander L. Greninger, MD, PhD, Cepheid: central contracts|Hologic: central contracts|Janssen: central contracts|Novavax: central contracts|Pfizer: central contracts Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant

Advax-CpG55.2-adjuvanted monovalent or trivalent SARS-CoV-2 recombinant spike protein vaccine protects hamsters against heterologous infection with Beta or Delta variants

The ongoing evolution of SARS-CoV-2 variants emphasizes the need for vaccines providing broad cross-protective immunity. This study was undertaken to assess the ability of Advax-CpG55.2 adjuvanted monovalent recombinant spike protein (Wuhan, Beta, Gamma) vaccines or a trivalent formulation to protect hamsters againstBeta or Delta virus infection. The ability of vaccines to block virus transmission to naïve co-housed animals was also assessed. In naïve hosts, the Beta variant induced higher virus loads than the Delta variant, and conversely the Delta variant caused more severe disease and was more likely to be associated with virus transmission. The trivalent vaccine formulation provided the best protection against both Beta and Delta infection and also completely prevented virus transmission. The next best performing vaccine was the original monovalent Wuhan-based vaccine. Notably, hamsters that received the monovalent Gamma spike vaccine had the highest viral loads and clinical disease of all the vaccine groups, a potential signal of antibody dependent-enhancement (ADE). These hamsters were also the most likely to transmit Delta virus to naïve recipients. In murine studies, the Gamma spike vaccine induced the highest total spike protein to RBD IgG ratio and the lowest levels of neutralizing antibody, a context that could predispose to ADE. Overall, the study results confirmed that the current SpikoGen® vaccine based on Wuhan spike protein was still able to protect against clinical disease caused by either the Beta or Delta virus variants but suggested additional protection may be obtained by combining it with extra variant spike proteins to make a multivalent formulation. This study highlights the complexity of optimizing vaccine protection against multiple SARS-CoV-2 variants and stresses the need to continue to pursue new and improved COVID-19 vaccines able to provide robust, long-lasting, and broadly cross-protective immunity against constantly evolving SARS-CoV-2 variants.

Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine

Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nanoparticle containing a blend of Spike, Membrane and Envelope antigens complexed for the first time with the RALA peptide (RALA-SME). The physicochemical characteristics and functionality of RALA-SME were assessed. With >99% encapsulation, RALA-SME was administered via intradermal injection in vivo, and all three antigen-specific IgG antibodies were highly significant. The IgG2a:IgG1 ratio were all >1.2, indicating a robust TH1 response, and this was further confirmed with the T-Cell response in mice. A complete safety panel of markers from mice were all within normal range, supported by safety data in hamsters. Vaccination of Syrian Golden hamsters with RALA-SME derivatives produced functional antibodies capable of neutralising SARS-CoV-2 from both Wuhan-Hu-1 and Omicron BA.1 lineages after two doses. Antibody levels increased over the study period and provided protection from disease-specific weight loss, with inhibition of viral migration down the respiratory tract. This peptide technology enables the flexibility to interchange and add antigens as required, which is essential for the next generation of adaptable mRNA vaccines.

Long-term safety and immunologic outcomes of daily oral immunotherapy for peanut allergy.

Oral immunotherapy containing peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) (Palforzia [Aimmune Therapeutics, Brisbane, Calif]) for 9 to 12 months resulted in higher tolerated amounts of peanut protein in PTAH-treated individuals aged 4 to 17 years with peanut allergy than in placebo-treated participants. We aimed to describe additional long-term pooled safety data and changes in peanut sensitization markers from baseline through approximately 5 years of treatment. The results from 6 clinical trials of PTAH (3 controlled and 3 open-label extension studies [N= 1227]) were pooled, and analysis of safety outcomes and immunologic data was performed. The PTAH doses were administered sequentially as follows: initial dose escalation (dose increased to 6 mg over 2 days), updosing (dose increased every 2 weeks to 300 mg for a minimum of 6 months), and maintenance dosing (300 mg per day). There was a trend toward decreased adverse events (AEs) at years 1 and 2 that was maintained up to 5 years, with 94% of patients experiencing mild or moderate AEs and only 13% discontinuing PTAH use because of AEs overall. Gastrointestinal symptoms were the most commonly reported treatment-related AEs. Adownward trend in systemic allergic reactions was also reported. PTAH treatment resulted in reduced levels of peanut-specific IgE after the first year and increased levels of peanut-specific IgG4, with a lowered peanut-specific IgE:IgG4 ratio. Areduction in median peanut skin prick test wheal diameter was observed (11.50 mm at baseline vs 5.75 mm at year 5). Long-term immunomodulation without any new safety signals was reported with PTAH immunotherapy in the largest safety data set and longest treatment duration for oral immunotherapy published to date.

One Health Approach in Serosurvey of Toxoplasma gondii in Former Black Slave (Quilombola) Communities in Southern Brazil and Among Their Dogs.

Brazilian quilombos are rural semi-isolated remnant communities of former black slaves and their descendants who traditionally maintained themselves through archaic subsistence livestock and agriculture practices and historically lacked specific public health policies. Although such individuals and their dogs may be exposed to zoonotic pathogens such as Toxoplasma gondii, no study to date has assessed these human-animal populations together. Populations in four different Brazilian quilombos in southern Brazil were evaluated. Overall, 93/208 people (44.7%) and 63/100 dogs (63.0%) were seropositive for IgG anti-T. gondii antibodies by indirect immunofluorescent antibody test (IFAT), 4/208 (1.9%) human samples seropositive for IgM anti-T. gondii antibodies, with a human-dog seropositivity ratio for IgG of 0.71. Quilombola individuals ingesting game meat were 2.43-fold more likely (95% CI: 1.05-5.9) to be seropositive. No risk factors were associated with seropositivity among dogs, thus suggesting that their exposure to T. gondii was random. Surprisingly, our research group had previously found an inverted human-dog ratio for T. gondii seropositivity of 2.54 in the urban area of a nearby major city. Because consumption of raw/undercooked game meat by quilombola individuals may have contributed to higher exposure, higher overall seroprevalence among dogs may have also indicated interaction with wildlife. Although these dogs may hunt wildlife without their owners' awareness, the higher dog seropositivity may also be related to feeding from discarded food in the community or backyard livestock animals and drinking surface water contaminated with oocysts. Thus, wildlife cannot be singled out as the reason, and future studies should consider sampling water, soil, wildlife, and livestock tissues, to fully establish the source of infection in dogs herein.

Immunogenicity and seroefficacy of 10-valent and 13-valent pneumococcal conjugate vaccines: a systematic review and network meta-analysis of individual participant data.

Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline, clinicaltrials.gov and trialsearch.who.int up to February 17, 2023 with no language restrictions. Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head-to-head randomised trials of young children under 2 years of age, and provided immunogenicity data for at least one time point after the primary vaccination series or the booster dose. Publication bias was assessed via Cochrane's Risk Of Bias due to Missing Evidence tool and comparison-adjusted funnel plots with Egger's test. Individual participant level data were requested from publication authors and/or relevant vaccine manufacturers. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and the relative risk (RR) of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Seroefficacy was defined as the RR of seroinfection. We also estimated the relationship between the GMR of IgG one month after priming and the RR of seroinfection by the time of the booster dose. The protocol is registered with PROSPERO, ID CRD42019124580. 47 studies were eligible from 38 countries across six continents. 28 and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14- to 1.54- fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Two-fold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (RR 0.46, 95% CI 0.23-0.96). Serotype-specific differences were found in immunogenicity and seroefficacy between PCV13 and PCV10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These findings could be used to compare PCVs and optimise vaccination strategies. The NIHR Health Technology Assessment Programme.

Impact of maternal SARS-CoV-2 booster vaccination on blood and breastmilk antibodies.

Maternal COVID-19 vaccination could protect infants who are ineligible for vaccine through antibody transfer during pregnancy and lactation. We measured the quantity and durability of SARS-CoV-2 antibodies in human milk and infant blood before and after maternal booster vaccination. Prospective cohort of lactating women immunized with primary and booster COVID-19 vaccines during pregnancy or lactation and their infants. Milk and blood samples from October 2021 to April 2022 were included. Anti-nucleoprotein (NP) and anti-receptor binding domain (RBD) IgG and IgA in maternal milk and maternal and infant blood were measured and compared longitudinally after maternal booster vaccine. Forty-five lactating women and their infants provided samples. 58% of women were anti-NP negative and 42% were positive on their first blood sample prior to booster vaccine. Anti-RBD IgG and IgA in milk remained significantly increased through 120-170 days after booster vaccine and did not differ by maternal NP status. Anti-RBD IgG and IgA did not increase in infant blood after maternal booster. Of infants born to women vaccinated in pregnancy, 74% still had positive serum anti-RBD IgG measured on average 5 months after delivery. Infant to maternal IgG ratio was highest for infants exposed to maternal primary vaccine during the second trimester compared to third trimester (0.85 versus 0.29; p<0.001). Maternal COVID-19 primary and booster vaccine resulted in robust and long-lasting transplacental and milk antibodies. These antibodies may provide important protection against SARS-CoV-2 during the first six months of life.

Assessing maternal and fetal SARS-CoV-2 viral load, antibody profiles and placental pathology following prenatal infection

Evaluate mother-to-infant transmission potential of SARS-CoV-2 and patterns of antibody transfer following prenatal infection. Prospective cohort of pregnant individuals infected with COVID-19. Samples collected at delivery included maternal swabs (nasopharyngeal/oropharyngeal, vaginal, anorectal), blood, breastmilk, newborn swabs (nasopharyngeal, sub-amniotic), amniotic fluid, cord blood, and placenta. Samples were analyzed by qPCR for SARS-CoV-2-RNA and IgG assays targeting the SARS-CoV-2 spike (S), nucleocapsid (N), and receptor binding domain (RBD) proteins. Placentas were evaluated for histologic lesions. The cohort included 213 individuals who delivered between from March 2020 to August 2021, and their 215 exposed offspring. SARS-CoV-2 was evident in maternal nasopharyngeal (64/145), vaginal (3/184) and anorectal (5/182) swabs and breastmilk (1/38). A total of 27/212 infants (12.7%) demonstrated evidence of mother-to-child transmission of SARS-CoV-2; SARS-CoV-2 was detected in nasopharyngeal swabs (21/142), amniotic fluid (3/77), sub-amniotic swabs (1/165), and placenta homogenates (6/138). Anti-SARS-CoV-2 IgA and IgM were detected in 1/189 neonates. Maternal and cord serum anti-RBD, anti-N and anti-S IgG were significantly and positively correlated ( R =0.26, 0.24, 0.23, respectively; P <0.05). Antibody transfer ratio of anti-RBD IgG was significantly correlated with weeks since maternal infection during pregnancy (R = 0.28, P <0.05). SARS-CoV-2 was detected in 6/138 placentas; placentas were characterized by acute (33/113), chronic inflammation (20/113), maternal (39/113) and fetal (12/113) vascular malperfusion. The rate of SARS-CoV-2 vertical transmission and transfer of maternal antibodies to newborn tissues was high. There were no pathological differences between infected placentas and controls. Further investigation into the timing of vertical transmission is warranted and its potential implications on offspring outcomes.