Additional Vaccine Research Articles

230.6: Ad.26.COV2.S Versus BNT162b2 or mRNA-1273 as a Third Dose in Solid Organ Transplant Recipients Seronegative After 2-dose mRNA Vaccination

Introduction: Heterologous vaccination (“mixing platforms”) for the third (D3) dose of SARS-CoV-2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed as to whether this provides any differential immunogenicity benefit. Method: We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA-1273; D3-mRNA) versus heterologous (Ad.26.COV2.S; D3-JJ) D3 among 377 SARS-CoV-2-infection naïve SOTRs who were seronegative after two mRNA vaccines. We measured anti-spike titers and used weighted (age and organ type) Poisson regression to evaluate prevalence of seroconversion and development of high-titers, comparing D3-JJ to D3-mRNA, at 1, 3 and 6-months post-D3. Titers measured after a fourth dose of vaccine, receipt of monoclonal antibodies, or SARS-CoV-2 infection were excluded from analyses. Results: 40 D3-JJ recipients and 337 D3-mRNA recipients were similar in sex, years since transplant, and mycophenolate use. At 1-month post-D3, 63% of D3-JJ recipients and 52% of D3-mRNA recipients became seropositive (p=0.28); this difference did not reach statistical significance in weighted analysis (weighted incidence-rate-ratio wIRR=0.981.291.69, p=0.064). High-titer response at 1-month post-D3 occurred in 29% of D3-JJ recipients and 25% of D3-mRNA recipients (p=0.7); this difference did not reach statistical significance in weighted analysis (wIRR=0.911.572.70, p=0.10). At 3-months post-D3, 80% of D3-JJ recipients and 57% of D3-mRNA recipients were seropositive (p=0.018); D3-JJ recipients were 1.4-fold more likely to be seropositive (wIRR=1.101.401.77, p0.006). High-titer response at 3-months post-D3 occurred in 27% of D3-JJ recipients and 22% of D3-mRNA recipients (p=0.64); this did not reach statistical significance (wIRR=0.440.921.93, p=0.8). At 6-months post-D3, 88% of D3-JJ recipients and 59% of D3-mRNA recipients were seropositive (p=0.026); D3-JJ recipients were 1.41-fold more likely to be seropositive (wIRR=1.041.411.93, p=0.029). High-titer response at 6-months post-D3 occurred in 59% of D3-JJ recipients and 21% of D3-mRNA recipients (p=0.005); D3-JJ recipients were 2.63-fold more likely to develop high-titers at 6-months post-D3 compared to D3-mRNA recipients (wIRR=1.382.635.00, p=0.003). Severe adverse reactions after D3 were rare; one D3-mRNA recipient reported fluid overload temporarily associated mRNA-1273. No D3-JJ recipients reported rejection before or after D3. Six D3-mRNA recipients reported acute rejection at median (IQR) 23 (12-131) days before D3. Conclusion: Heterologous vaccination with Ad.26.COV2.S for D3 was associated with higher late seroconversion than homologous vaccination with a third mRNA dose among SOTRs negative after a 2-dose mRNA series. SOTRs with persistent negative sero-response to mRNA vaccine series might benefit from Ad.26.COV2.S as an additional vaccine dose. Ben-Dov family. Trokhan Patternson family. 5T32DK007713 (Dr. Alejo). ASTS Fryer Resident Scientist Award (Dr. Mitchell). K01DK101677 (Dr. Massie). K23DK115908 (Dr. Garonzik-Wang). K24AI144954 (Dr. Segev). U01AI138897 (Dr. Werbel). K23AI157893 (Dr. Werbel). DL Segev has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, Thermo Fisher Scientific, Regeneron, and AstraZeneca. Dr. Levan is the Social Media Editor for Transplantation. Dr. Avery has grant/research support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, and Takeda/Shire. The remaining authors of this manuscript have no financial disclosures or conflicts of interest to disclose.

Assessment of Predictors for SARS-CoV-2 Antibodies Decline Rate in Health Care Workers after BNT162b2 Vaccination-Results from a Serological Survey.

Background: SARS-CoV-2 is a novel human pathogen causing Coronavirus Disease 2019 that has caused widespread global mortality and morbidity. Since health workers in Israel were among the first to be vaccinated, we had a unique opportunity to investigate the post-vaccination level of IgG anti-S levels antibodies (Abs) and their dynamics by demographic and professional factors. Methods: Prospective Serological Survey during December 2020–August 2021 at Barzilai Medical Center among 458 health care workers (HCW) followed for 6 months after the second BNT162b2 vaccine dose. Results: Antibody levels before the second dose, and 30, 90 and 180 days after were 57.1 ± 29.2, 223 ± 70.2, 172.8 ± 73.3 and 166.4 ± 100.7 AU/mL, respectively. From GEE analysis, females had higher Abs levels (β = 26.37 AU/mL, p = 0.002). Age was negatively associated with Abs, with a 1.17 AU/mL decrease for each additional year (p < 0.001). Direct contact with patients was associated with lower Abs by 25.02 AU/mL (p = 0.009) compared to working with no such contact. The average decline rate overall for the study period was 3.0 ± 2.9 AU/mL per week without differences by demographic parameters and was faster during the first 3 months after vaccination than in the subsequent 3 months. Conclusions: All demographic groups experienced a decline in Abs over time, faster during the first 3 months. Findings of overall Abs lower in males, workers with direct contact with patients, and older workers, should be considered for policy-making about choosing priority populations for additional vaccine doses in hospital settings.

Advances in Research on COVID-19 Vaccination for People Living with HIV.

Advances in Research on COVID-19 Vaccination for People Living with HIV.

Third Early "Booster" Dose Strategy in France of bnt162b2 SARS-CoV-2 Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients Enhances Neutralizing Antibody Responses.

Immunocompromised individuals generally fail to mount efficacious immune humoral responses following vaccination. The emergence of SARS-CoV-2 variants of concern has raised the question as to whether levels of anti-spike protein antibodies achieved after two or three doses of the vaccine efficiently protect against breakthrough infection in the context of immune suppression. We used a fluorescence-based neutralization assay to test the sensitivity of SARS-CoV-2 variants (ancestral variant, Beta, Delta, and Omicron BA.1) to the neutralizing response induced by vaccination in highly immunosuppressed allogeneic HSCT recipients, tested after two and three doses of the BNT162b2 vaccine. We show that neutralizing antibody responses to the Beta and Delta variants in most immunocompromised HSCT recipients increased after three vaccine doses up to values similar to those observed in twice-vaccinated healthy adults and were significantly lower against Omicron BA.1. Overall, neutralization titers correlated with the amount of anti-S-RBD antibodies measured by means of enzyme immunoassay, indicating that commercially available assays can be used to quantify the anti-S-RBD antibody response as a reliable surrogate marker of humoral immune protection in both immunocompetent and immunocompromised individuals. Our findings support the recommendation of additional early vaccine doses as a booster of humoral neutralizing activity against emerging variants, in HSCT immunocompromised patients. In the context of Omicron circulation, it further emphasizes the need for reinforcement of preventive measures including the administration of monoclonal antibodies in this high-risk population.

Potential for false decline of anti-SARS-CoV-2 spike antibody titers after COVID-19 vaccination.

We read the Comment by Amit Saxena and colleagues1 regarding the clinical efficacy and seroreactivity of an additional COVID-19 vaccine dose in patients with systemic lupus erythematosus with great interest.1 Samples were analysed at a mean of 44·7 days (SD 31·7) after the additional dose, and rates of breakthrough infections and anti-SARS-CoV-2 spike protein antibody titres were compared between those who did and did not receive an additional vaccine dose after the initial vaccination series. Although there were fewer breakthrough infections after the additional vaccine dose, there was no association between the antibody titre reported after that vaccine dose and infection.

A personal COVID-19 dendritic cell vaccine made at point-of-care: Feasibility, safety, and antigen-specific cellular immune responses

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a world-wide pandemic. Internationally, because of availability, accessibility, and distribution issues, there is a need for additional vaccines. This study aimed to: establish the feasibility of personal dendritic cell vaccines to the SARS-CoV-2 spike protein, establish the safety of a single subcutaneous vaccine injection, and determine the antigen-specific immune response following vaccination. In Phase 1, 31 subjects were assigned to one of nine formulations of autologous dendritic cells and lymphocytes (DCL) incubated with 0.10, 0.33, or 1.0 µg of recombinant SARS-CoV-2 spike protein, and admixed with saline or 250 or 500 µg of granulocyte-macrophage colony-stimulating factor (GM-CSF) prior to injection, then assessed for safety and humoral response. In Phase 2, 145 subjects were randomized to one of three formulations defined by incubation with the same three quantities of spike protein without GM-CSF, then assessed for safety and cellular response. Vaccines were successfully manufactured for every subject at point-of-care. Approximately 46.4% of subjects had a grade 1 adverse event (AE); 6.5% had a grade 2 AE. Among 169 evaluable subjects, there were no acute allergic, grade 3 or 4, or serious AE. In Phase 1, anti-receptor binding domain antibodies were increased in 70% of subjects on day-28. In Phase 2, in the 127 subjects who did not have high levels of gamma interferon-producing cells at baseline, 94.4% had increased by day 14 and 96.8% by day 28. Point-of-care personal vaccine manufacturing was feasible. Further development of such subject-specific vaccines is warranted.

Leveraging meatpacking ownership concentration and community centrality to improve disease resiliency

The U.S. meat processing sector has been subject to amplified scrutiny after workers exhibited disproportionately high rates of COVID-19 infections and deaths. In response, Tyson Foods—one of the largest meat packers in the country—mandated that its employees be vaccinated against COVID-19 by November 1, 2021. In this paper, we investigate the impact that the Tyson vaccine mandate had on vaccine uptake, infection rates, and deaths in counties where Tyson processing facilities are located. We find that the mandate resulted in approximately 35,000 additional vaccinations. The resultant vaccine uptake avoided 98 COVID-19 infections per day and nearly 75 COVID-19-related deaths; the associated public health savings total $45.4 million. Employee health-related interventions at the corporate level can leverage industry ownership concentration and the centrality of packing operations in host communities to improve health outcomes and disease resiliency well beyond the packing operations.

Easy Scheme Outlining the Various Morphological and Vascular Abnormalities of the Lymph Node Structure Associated with Recent COVID-19 Vaccination, Each with a Different Clinical/Diagnostic Management.

Throughout this recent ongoing SARS-CoV-2 pandemic, the European Society of Breast Imaging have surely contributed in improving the management of unilateral axillary adenopathy appearance homolaterally to the side of vaccine inoculation. After considering the patient’s COVID-19 history of vaccination, our group produced a day-to-day scheme that evaluates meticulously the probability of mammary malignancy, according to the lymph node characteristics including vascular abnormalities. It comprises of a UN (ultrasound node) score ranging from 2 to 5, that increases with the suspicion of malignancy. In this setting and in view of the additional incoming COVID-19 boost-dose vaccinations, we believe our model could be of great utility to radiologist when assessing patients whom do not have a straight forward diagnosis, in order to reduce breast cancer missed diagnosis, avoid delaying vaccinations, reduce rescheduling of breast imaging examinations and lastly avoid unnecessary lymph node biopsies.

Multimerization of Ebola GPΔmucin on protein nanoparticle vaccines has minimal effect on elicitation of neutralizing antibodies.

Ebola virus (EBOV), a member of the Filoviridae family of viruses and a causative agent of Ebola Virus Disease (EVD), is a highly pathogenic virus that has caused over twenty outbreaks in Central and West Africa since its formal discovery in 1976. The only FDA-licensed vaccine against Ebola virus, rVSV-ZEBOV-GP (Ervebo®), is efficacious against infection following just one dose. However, since this vaccine contains a replicating virus, it requires ultra-low temperature storage which imparts considerable logistical challenges for distribution and access. Additional vaccine candidates could provide expanded protection to mitigate current and future outbreaks. Here, we designed and characterized two multimeric protein nanoparticle subunit vaccines displaying 8 or 20 copies of GPΔmucin, a truncated form of the EBOV surface protein GP. Single-dose immunization of mice with GPΔmucin nanoparticles revealed that neutralizing antibody levels were roughly equivalent to those observed in mice immunized with non-multimerized GPΔmucin trimers. These results suggest that some protein subunit antigens do not elicit enhanced antibody responses when displayed on multivalent scaffolds and can inform next-generation design of stable Ebola virus vaccine candidates.

Humoral response to SARS-CoV-2 mRNA vaccination in previous non-responder kidney transplant recipients after short-term withdrawal of mycophenolic acid.

Seroconversion rates after COVID-19 vaccination are significantly lower in kidney transplant recipients compared to healthy cohorts. Adaptive immunization strategies are needed to protect these patients from COVID-19. In this prospective observational cohort study, we enrolled 76 kidney transplant recipients with no seroresponse after at least three COVID-19 vaccinations to receive an additional mRNA-1273 vaccination (full dose, 100 μg). Mycophenolic acid was withdrawn in 43 selected patients 5–7 days prior to vaccination and remained paused for 4 additional weeks after vaccination. SARS-CoV-2-specific antibodies and neutralization of the delta and omicron variants were determined using a live-virus assay 4 weeks after vaccination. In patients with temporary mycophenolic acid withdrawal, donor-specific anti-HLA antibodies and donor-derived cell-free DNA were monitored before withdrawal and at follow-up. SARS-CoV-2 specific antibodies significantly increased in kidney transplant recipients after additional COVID-19 vaccination. The effect was most pronounced in individuals in whom mycophenolic acid was withdrawn during vaccination. Higher SARS-CoV-2 specific antibody titers were associated with better neutralization of SARS-CoV-2 delta and omicron variants. In patients with short-term withdrawal of mycophenolic acid, graft function and donor-derived cell-free DNA remained stable. No acute rejection episode occurred during short-term follow-up. However, resurgence of prior anti-HLA donor-specific antibodies was detected in 7 patients.

Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian multiple sclerosis patients, a follow-up study.

Monitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) help to establish the optimal strategies to ensure adequate COVID-19 protection without compromising disease control offered by DMTs. Following our previous observations on the humoral response one month after two doses of BNT162b2 vaccine (T1) in MS patients differently treated, here we present a cross-sectional and longitudinal follow-up analysis six months following vaccination (T2, n=662) and one month following the first booster (T3, n=185). Consistent with results at T1, humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients also at the time points considered here (T2 and T3). Interestingly, a strong upregulation one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. Although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT.

Parental perceptions and the 5C psychological antecedents of COVID-19 vaccination during the first month of omicron variant surge: A large-scale cross-sectional survey in Saudi Arabia.

BackgroundWith the rapid surge of SARS-CoV-2 Omicron variant, we aimed to assess parents' perceptions of the COVID-19 vaccines and the psychological antecedents of vaccinations during the first month of the Omicron spread.MethodsA cross-sectional online survey in Saudi Arabia was conducted (December 20, 2021-January 7, 2022). Convenience sampling was used to invite participants through several social media platforms, including WhatsApp, Twitter, and email lists. We utilized the validated 5C Scale, which evaluates five psychological factors influencing vaccination intention and behavior: confidence, complacency, constraints, calculation, and collective responsibility.ResultsOf the 1,340 respondents, 61.3% received two doses of the COVID-19 vaccine, while 35% received an additional booster dose. Fify four percentage were unwilling to vaccinate their children aged 5–11, and 57.2% were unwilling to give the additional booster vaccine to children aged 12–18. Respondents had higher scores on the construct of collective responsibility, followed by calculation, confidence, complacency, and finally constraints. Confidence in vaccines was associated with willingness to vaccinate children and positively correlated with collective responsibility (p < 0.010). Complacency about COVID-19 was associated with unwillingness to vaccinate older children (12–18 years) and with increased constraints and calculation scores (p < 0.010). While increasing constraints scores did not correlate with decreased willingness to vaccinate children (p = 0.140), they did correlate negatively with confidence and collective responsibility (p < 0.010).ConclusionsThe findings demonstrate the relationship between the five antecedents of vaccination, the importance of confidence in vaccines, and a sense of collective responsibility in parents' intention to vaccinate their children. Campaigns addressing constraints and collective responsibility could help influence the public's vaccination behavior.

Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities.

New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. This review provides an overview of protein-based adjuvants (PBAs) obtained from different organisms, including bacteria, mollusks, plants, and humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- and T-cell-mediated immune responses to administered antigens, providing advantages over many currently adopted adjuvant approaches. Furthermore, PBAs are natural biocompatible and biodegradable substances that induce minimal reactogenicity and toxicity and interact with innate immune receptors, enhancing their endocytosis and modulating subsequent adaptive immune responses. We propose that PBAs can contribute to the development of vaccines against complex pathogens, including intracellular pathogens such as Mycobacterium tuberculosis, those with complex life cycles such as Plasmodium falciparum, those that induce host immune dysfunction such as HIV, those that target immunocompromised individuals such as fungi, those with a latent disease phase such as Herpes, those that are antigenically variable such as SARS-CoV-2 and those that undergo continuous evolution, to reduce the likelihood of outbreaks.

Head-to-head comparison of the immunogenicity of RotaTeq and Rotarix rotavirus vaccines and factors associated with seroresponse in infants in Bangladesh: a randomised, controlled, open-label, parallel, phase 4 trial

A head-to-head comparison of the most widely used oral rotavirus vaccines has not previously been done, particularly in a high child mortality setting. We therefore aimed to compare the immunogenicity of RotaTeq (Merck, Kenilworth, NJ, USA) and Rotarix (GlaxoSmithKline, Rixensart, Belgium) rotavirus vaccines in the same population and examined risk factors for low seroresponse. We did a randomised, controlled, open-label, parallel, phase 4 trial in urban slums within Mirpur and Mohakahli (Dhaka, Bangladesh). We enrolled eligible participants who were healthy infants aged 6 weeks and full-term (ie, &gt;37 weeks' gestation). We randomly assigned participants (1:1), using block randomisation via a computer-generated electronic allocation with block sizes of 8, 16, 24, and 32, to receive either three RotaTeq vaccine doses at ages 6, 10, and 14 weeks or two Rotarix doses at ages 6 and 10 weeks without oral poliovirus vaccine. Coprimary outcomes were the rotavirus-specific IgA seroconversion in both vaccines, and the comparison of the rotavirus IgA seroconversion by salivary secretor phenotype in each vaccine arm. Seroconversion at age 18 weeks in the RotaTeq arm and age of 14 weeks in the Rotarix arm was used to compare the complete series of each vaccine. Seroconversion at age 14 weeks was used to compare two RotaTeq doses versus two Rotarix doses. Seroconversion at age 22 weeks was used to compare the immunogenicity at the same age after receiving the full vaccine series. Safety was assessed for the duration of study participation. This study is registered with ClinicalTrials.gov, NCT02847026. Between Sept 1 and Dec 8, 2016, a total of 1144 infants were randomly assigned to either the RotaTeq arm (n=571) or Rotarix arm (n=573); 1080 infants (531 in the RotaTeq arm and 549 in the Rotarix arm) completed the study. Rotavirus IgA seroconversion 4 weeks after the full series occurred in 390 (73%) of 531 infants age 18 weeks in the RotaTeq arm and 354 (64%) of 549 infants age 14 weeks in the Rotarix arm (p=0·01). At age 14 weeks, 4 weeks after two doses, RotaTeq recipients had lower seroconversion than Rotarix recipients (268 [50%] of 531 vs 354 [64%] of 549; p&lt;0·0001). However, at age 22 weeks, RotaTeq recipients had higher seroconversion than Rotarix recipients (394 [74%] of 531 vs 278 [51%] of 549; p&lt;0·0001). Among RotaTeq recipients, seroconversion 4 weeks after the third dose was higher than after the second dose (390 [73%] of 531 vs 268 [50%] of 531; p&lt;0·0001]. In the RotaTeq arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·08), 18 weeks (p=0·01), and 22 weeks (p=0·02). Similarly, in the Rotarix arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·02) and 22 weeks (p=0·01). 65 (11%) of 571 infants had adverse events in the RotaTeq arm compared with 63 (11%) of 573 infants in the Rotarix arm; no adverse events were attributed to the use of either vaccine. One death due to aspiration occurred in the RotaTeq arm, which was not related to the vaccine. RotaTeq induced a higher magnitude and longer duration of rotavirus IgA response than Rotarix in this high child mortality setting. Additional vaccination strategies should be evaluated to overcome the suboptimal performance of current oral rotavirus vaccines in these settings. US Centers for Disease Control and Prevention.

Intensity and longevity of SARS-CoV-2 vaccination response in patients with immune-mediated inflammatory disease: a prospective cohort study.

BackgroundConcerns have been raised about the reduced immunogenicity of vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory diseases and the higher risk of breakthrough infections. The objective of our study was to investigate the intensity and longevity of SARS-CoV-2 vaccination responses in patients with immune-mediated inflammatory diseases, and to assess the effects of diagnosis, treatment, and adapted vaccination schedules.MethodsSARS-CoV-2 IgG antibody response after SARS-CoV-2 vaccination was measured over time in a large prospective cohort of healthy controls and participants with immune-mediated inflammatory diseases (attending or admitted to affiliated centres) between Dec 15, 2020, and Dec 1, 2021. Cohort participants with immune-mediated inflammatory diseases and control participants with no diagnosis of immune-mediated inflammatory diseases, were eligible for this analysis. Demographic data and disease-specific data were collected using a questionnaire. Humoral response was compared across treatment and disease groups, and with respect to the receipt of additional vaccinations. SARS-CoV-2 antibody response was measured by ELISA using optical density ratio units and modelled over time with age and sex adjustment using mixed-effects models. Using these models, marginal mean antibody titres and marginal risks of a poor response (optical density ratio <1·1) were calculated for each week starting from week 8 after the first vaccination to week 40.FindingsAmong 5076 individuals registered, 2535 participants with immune-mediated inflammatory diseases (mean age 55·0 [15·2] years; 1494 [58·9%] women and 1041 [41·1%] men) and 1198 healthy controls (mean age 40·7 [13·5] years; 554 [46·2%] women and 644 [53·8%] men) were included in this analysis. Mean antibody titres were higher in healthy controls compared with people with immune-mediated inflammatory diseases at all timepoints, with a peak antibody response in healthy controls (mean optical density ratio 12·48; 95% CI 11·50–13·53) of more than twice that in participants with immune-mediated inflammatory diseases (5·50; 5·23–5·77; mean difference 6·98; 5·92–8·04). A poor response to vaccination was observed in participants with immune-mediated inflammatory diseases who were taking B-cell inhibitors (peak mean difference from healthy controls 11·68; 10·07–13·29) and T-cell inhibitors (peakmean difference from healthy controls 10·43; 8·33–12·53). Mean differences in antibody responses between different immune-mediated inflammatory diseases were small. Participants with immune-mediated inflammatory diseases who were given a third vaccine dose had higher mean antibody titres than did healthy controls vaccinated with two vaccine doses at 40 weeks after the initial vaccination (mean difference 1·34; 0·01–2·69).InterpretationPeople with immune-mediated inflammatory diseases show a lower and less durable SARS-CoV-2 vaccination response and are at risk of losing humoral immune protection. Adjusted vaccination schedules with earlier booster doses or more frequent re-doses, or both, could better protect people with immune-mediated inflammatory diseases.FundingDeutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, European Research Council, Innovative Medicine Initiative, Friedrich-Alexander-Universität Erlangen-Nürnberg, Else Kröner-Memorial Foundation.

Analysis of Factors Affecting Neutralizing Antibody Production after COVID-19 Vaccination Using Newly Developed Rapid Point-of-Care Test.

(1) Objective: To investigate the factors that affect rates of neutralizing antibody production and duration after vaccination using the newly developed SARS-CoV-2 POCT. (2) Methods: The production of immunoglobulin and neutralizing antibody in clinical subjects who completed various vaccines was analyzed using the POCT, the semi-quantitative was interpreted by measurement application, and the quantified neutralizing antibody titers were using the ELISA. (3) Results: According to the clinical performance analysis of the POCT, the clinical sensitivity and the specificity were 96.8% (90/93) and 97.7% (167/171), respectively, for the S1 RBD IgG antibody. The clinical sensitivity was 92.22% (83/90), and the clinical specificity was 100.00% (174/174) for neutralizing antibodies. Factors influencing antibody production were analyzed using the whole blood of the five types of second-completed vaccinators (N = 736, 20–80 years old). General and neutralizing antibody and showed significant differences in age (p < 0.0001), vaccine type (p < 0.0001), inoculation interval (p < 0.0001), pain score (p < 0.0001), diabetes (p < 0.0001), and hypertension (p = 0.002). The gender (p = 0.021) and chronic fatigue (p = 0.02) did not show the significance. (4) Conclusions: An acquisition of immunoglobulin and neutralizing antibody varies according to vaccine type, age, days after vaccination, pain degree after vaccination, and underlying diseases. The POCT used in this study will be utilized for clinical recommendations such as deciding whether to receive additional vaccines through the immediate rapid determination of neutralizing antibody generation in the clinical site.

Analysis of the humoral and cellular response after the third COVID-19 vaccination in patients with autoimmune hepatitis.

Background & AimsTo explore the humoral and T‐cell response to the third COVID‐19 vaccination in autoimmune hepatitis (AIH).MethodsAnti‐SARS‐CoV‐2 antibody titers were prospectively determined in 81 AIH patients and 53 healthy age‐ and sex‐matched controls > 7 days (median 35) after the first COVID‐19 booster vaccination. The spike‐specific T‐cell response was assessed using an activation‐induced marker assay (AIM) in a subset of patients.ResultsMedian antibody levels were significantly lower in AIH compared to controls (10908 vs. 25000 AU/mL, p<0.001), especially in AIH patients treated with MMF (N=14, 4542 AU/mL, p=0.004) or steroids (N=27, 7326 AU/mL, p=0.020). Also, 48% of AIH patients had antibody titers below the 10% percentile of the healthy controls (9194 AU/mL, p<0.001). AIH patients had a high risk of failing to develop a spike‐specific T‐cell response (15/34 (44%) vs. 2/16 (12%), p=0.05) and showed overall lower frequencies of spike‐specific CD4+T cells (median: 0.074% vs 0.283;p=0.01) after the booster vaccination compared to healthy individuals. In 34/81 patients, antibody titers before and after booster vaccination were available. In this subgroup, all patients but especially those without detectable/low antibodies titers (<100 AU/mL) after the second vaccination (N=11/34) showed a strong, 148‐fold increase.ConclusionA third COVID‐19 vaccination efficiently boosts antibody levels and T‐cell responses in AIH patients and even seroconversion in patients with absent immune response after two vaccinations, but to a lower level compared to controls. Therefore, we suggest routinely assessing antibody levels in AIH patients and offering additional booster vaccinations to those with suboptimal response.

Patents vs pandemics

The COVID-19 pandemic has forced a rethinking of public health and patent systems. It has brought livelihoods to a halt, wreaking havoc on people's lives and national economies. The need to create and deploy additional vaccinations, repurpose pharmaceuticals, and sustain medical infrastructure is jeopardising global health security. At the international and national levels, collaboration and collaborative action are essential. In terms of public health, IPR access is critical. Many countries have announced new rules and passed legislation to make it simpler to provide medicines to their citizens during the pandemic. Compulsory licensing has been a key tool for opening up IP without the approval of patent holders.There is frequently a conflict between the need to grant monopolies in the form of IP rights as an incentive for pharmaceutical sector advancements on the one hand, and the need to award monopolies in the form of IP rights as a fundamental right on the other. As a result, hurdles exist in decision-making in order to strike a balance between innovative incentives and assuring access to healthcare.

Cost-effectiveness of rotavirus vaccination in Mozambique

IntroductionRotavirus is one of the most common cause of severe gastroenteritis in children, with the largest mortality burden in low- and middle-income countries. To prevent rotavirus gastroenteritis, Mozambique introduced ROTARIX® vaccine in 2015, however, its cost-effectiveness has never been established in the country. In 2018, additional vaccines became available globally. This study estimates the cost-effectiveness of the recently introduced ROTARIX in Mozambique and compares the cost-effectiveness of ROTARIX®, ROTAVAC®, and ROTASIIL® to inform future use. MethodsWe used a decision-support model to calculate the potential cost-effectiveness of vaccination with ROTARIX compared to no vaccination over a five-year period (2016–2020) and to compare the cost-effectiveness of ROTARIX, ROTAVAC, and ROTASIIL to no vaccination and to each other over a ten-year period (2021–2030). The primary outcome was the incremental cost per disability-adjusted life-year (DALY) averted from a government perspective. We assessed uncertainty through sensitivity analyses. ResultsFrom 2016 to 2020, we estimate the vaccine program with ROTARIX cost US$12.3 million, prevented 4,628 deaths, and averted US$3.1 million in healthcare costs. The cost per DALY averted was US$70. From 2021 to 2030, we estimate all three vaccines could prevent 9,000 deaths and avert US$7.8 million in healthcare costs. With Global Alliance for Vaccines and Immunization (Gavi) support, ROTARIX would have the lowest vaccine program cost (US$31 million) and 98 % probability of being cost-effective at a willingness-to-pay threshold of 0.5x GDP per capita. Without Gavi support, ROTASIIL would have the lowest vaccine program cost (US$75.8 million) and 30 % probability of being cost-effective at the same threshold. ConclusionROTARIX vaccination had a substantial public health impact in Mozambique between 2016 and 2020. ROTARIX is currently estimated to be the most cost-effective product, but the choice of vaccine should be re-evaluated as more evidence emerges on the price, incremental delivery cost, wastage, and impact associated with each of the different rotavirus vaccines.

The Adverse Reactions of Pfizer BioNTech COVID-19 Vaccine Booster Dose are Mild and Similar to the Second Dose Responses: A Retrospective Cross-Sectional Study.

BackgroundLike other vaccines, Pfizer BioNTech’s COVID-19 vaccine efficacy against SARS-CoV-2 virus infections begins to decline within a few months after the 2nd dose. On August 12, 2021, the FDA allowed additional Pfizer BioNTch’s COVID-19 vaccine dose (3rd or booster dose) for individuals with weakened immunity. This study aimed to evaluate the short-term adverse reactions (ADRs) of the 2nd and the 3rd doses of the Pfizer BioNTech COVID-19 vaccine.MethodsInformation for this study was collected by Google Form questionnaire (online survey). The results included responses from 442 people, the majority from Saudi Arabia.ResultsThe most common local ADRs following the 3rd dose were injection site pain, injection site hypersensitivity, and axillary lymph node swelling. The most common systemic ADRs were fatigue, muscle pain, bone pain, headache, and fever less than 38ºC. Less common systemic ADRs were shivering, fever more than 38ºC, nasal congestion and rhinorrhea, arrhythmia, cough, abdominal pain, chest tightness, nausea, diarrhea, vomiting, and tachypnea. Rare systemic ADRs were constipation, dizziness and vertigo, lack of concentration, sore throat, excessive hair loss, dysmenorrhea and heavy menstruation, and Bell’s palsy. Severe allergic reactions were reported by 2.6% of participants after the 2nd dose, compared with none after the 3rd dose. Nasal congestion and runny nose are more frequent after the 3rd dose. The ADRs of the 2nd and 3rd doses were significantly more prevalent in females. 12% of participants reported ADRs lasting more than one week after the 3rd dose compared to 5% after the 2nd dose. People ≤ 60 years were more affected by the vaccine ADRs.ConclusionMost of the ADRs reported after the 3rd vaccine dose were consistent with the Pfizer vaccine information sheet and similar to the 2nd dose ADRs.