Innate protection against intrarectal SIV acquisition by a live SHIV vaccine.

Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection against SIV/HIV (SHIV) acquisition. Here, we evaluated the efficacy of an SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded, as there was no cross-reactivity between SIV and SHIV envelope antibodies. After 8 low-dose intrarectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated efficacy, compared with 6 naive controls, suggesting protection was achieved in the absence of anti-envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for preventing viral acquisition, as none of the CD8-depleted macaques were infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity, identified mechanisms, and may provide opportunities for novel HIV vaccines or therapeutic strategy development.

Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques.

The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls and women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian immunodeficiency virus (SIV)mac251 acquisition is reduced by more than 90% using a combination of a vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment of the zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures to the highly pathogenic SIVmac251, 80% of a cohort of 20 macaques vaccinated and treated with SAMT-247 remained uninfected. In an arm of 18 vaccinated-only animals without microbicide, 40% of macaques remained uninfected. The combined SAMT-247/vaccine regimen was significantly more effective than vaccination alone. By analysing immune correlates of protection, we show that, by increasing zinc availability, SAMT-247 increases natural killer cytotoxicity and monocyte efferocytosis, and decreases T-cell activation to augment vaccine-induced protection.

Booster vaccination is required to elicit and maintain COVID-19 vaccine-induced immunity in SIV-infected macaques.

ABSTRACTProlonged infection and possible evolution of SARS-CoV-2 in patients living with uncontrolled HIV-1 infection highlight the importance of an effective vaccination regimen, yet the immunogenicity of COVID-19 vaccines and predictive immune biomarkers have not been well investigated. Herein, we report that the magnitude and persistence of antibody and cell-mediated immunity (CMI) elicited by an Ad5-vectored COVID-19 vaccine are impaired in SIV-infected macaques with high viral loads (> 105 genome copies per ml plasma, SIVhi) but not in macaques with low viral loads (< 105, SIVlow). After a second vaccination, the immune responses are robustly enhanced in all uninfected and SIVlow macaques. These responses also show a moderate increase in 70% SIVhi macaques but decline sharply soon after. Further analysis reveals that decreased antibody and CMI responses are associated with reduced circulating follicular helper T cell (TFH) counts and aberrant CD4/CD8 ratios, respectively, indicating that dysregulation of CD4+ T cells by SIV infection impairs the COVID-19 vaccine-induced immunity. Ad5-vectored COVID-19 vaccine shows no impact on SIV loads or SIV-specific CMI responses. Our study underscores the necessity of frequent booster vaccinations in HIV-infected patients and provides indicative biomarkers for predicting vaccination effectiveness in these patients.

Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques.

HIV vaccine mediated efficacy, using an expanded live attenuated recombinant varicella virus-vectored SIV rSVV-SIVgag/env vaccine prime with adjuvanted SIV-Env and SIV-Gag protein boosts, was evaluated in a female rhesus macaques (RM) model against repeated intravaginal SIV challenges. Vaccination induced anti-SIV IgG responses and neutralizing antibodies were found in all vaccinated RMs. Three of the eight vaccinated RM remained uninfected (vaccinated and protected, VP) after 13 repeated challenges with the pathogenic SIVmac251-CX-1. The remaining five vaccinated and infected (VI) macaques had significantly reduced plasma viral loads compared with the infected controls (IC). A significant increase in systemic central memory CD4+ T cells and mucosal CD8+ effector memory T-cell responses was detected in vaccinated RMs compared to controls. Variability in lymph node SIV-Gag and Env specific CD4+ and CD8+ T cell cytokine responses were detected in the VI RMs while all three VP RMs had more durable cytokine responses following vaccination and prior to challenge. VI RMs demonstrated predominately SIV-specific monofunctional cytokine responses while the VP RMs generated polyfunctional cytokine responses. This study demonstrates that varicella virus-vectored SIV vaccination with protein boosts induces a 37.5% efficacy rate against pathogenic SIV challenge by generating mucosal memory, virus specific neutralizing antibodies, binding antibodies, and polyfunctional T-cell responses.

Transient T Cell Expansion, Activation, and Proliferation in Therapeutically Vaccinated Simian Immunodeficiency Virus-Positive Macaques Treated with N-803.

Vaccine strategies aimed at eliciting human immunodeficiency virus (HIV)-specific CD8+ T cells are one major target of interest in HIV functional cure strategies. We hypothesized that CD8+ T cells elicited by therapeutic vaccination during antiretroviral therapy (ART) would be recalled and boosted by treatment with the interleukin 15 (IL-15) superagonist N-803 after ART discontinuation. We intravenously immunized four simian immunodeficiency virus-positive (SIV+) Mauritian cynomolgus macaques receiving ART with vesicular stomatitis virus (VSV), modified vaccinia virus Ankara strain (MVA), and recombinant adenovirus serotype 5 (rAd-5) vectors all expressing SIVmac239 Gag. Immediately after ART cessation, these animals received three doses of N-803. Four control animals received no vaccines or N-803. The vaccine regimen generated a high-magnitude response involving Gag-specific CD8+ T cells that were proliferative and biased toward an effector memory phenotype. We then compared cells elicited by vaccination (Gag specific) to cells elicited by SIV infection and unaffected by vaccination (Nef specific). We found that N-803 treatment enhanced the frequencies of both bulk and proliferating antigen-specific CD8+ T cells elicited by vaccination and the antigen-specific CD8+ T cells elicited by SIV infection. In sum, we demonstrate that a therapeutic heterologous prime-boost-boost (HPBB) vaccine can elicit antigen-specific effector memory CD8+ T cells that are boosted by N-803. IMPORTANCE While antiretroviral therapy (ART) can suppress HIV replication, it is not a cure. It is therefore essential to develop therapeutic strategies to enhance the immune system to better become activated and recognize virus-infected cells. Here, we evaluated a novel therapeutic vaccination strategy delivered to SIV+ Mauritian cynomolgus macaques receiving ART. ART was then discontinued and we delivered an immunotherapeutic agent (N-803) after ART withdrawal with the goal of eliciting and boosting anti-SIV cellular immunity. Immunologic and virologic analysis of peripheral blood and lymph nodes collected from these animals revealed transient boosts in the frequency, activation, proliferation, and memory phenotype of CD4+ and CD8+ T cells following each intervention. Overall, these results are important in educating the field of the transient nature of the immunological responses to this particular therapeutic regimen and the similar effects of N-803 on boosting T cells elicited by vaccination or elicited naturally by infection.

TGF-ß-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine.

TGF-ß signaling is necessary for CD8+ T cell differentiation into tissue resident memory T cells (TRM). Although higher frequency of CD8+ TRM cells in the tumor microenvironment is associated with better prognosis, TGF-ß-blockade typically improves rather than worsens outcomes. Here we show that in a mouse melanoma model, in the tumor-draining lymph nodes (TDLN) rather than in the tumors themselves, stem-like CD8+ T cells differentiate into TRMs in a TGF-ß and tumor antigen dependent manner. Following vaccination against a melanoma-specific epitope, most tumour-specific CD8+ T cells are maintained in a stem-like state, but a proportion of cells lost TRM status and differentiate into CX3CR1+ effector CD8+ T cells in the TDLN, which are subsequently migrating into the tumours. Disruption of TGF-ß signaling changes the dynamics of these developmental processes, with the net result of improving effector CD8+ T cell migration into the tumours. In summary, TDLN stem-like T cells transiently switch from a TGF-ß-dependent TRM differentiation program to an anti-tumor migratory effector development upon vaccination, which transition can be facilitated by targeted TGF-ß blockade.

Vaccine breakthrough infection leads to distinct profiles of neutralizing antibody responses by SARS-CoV-2 variant.

Protective immunity against SARS-CoV-2 infection after COVID-19 vaccination may differ by variant. We enrolled vaccinated (n = 39) and unvaccinated (n = 11) individuals with acute, symptomatic SARS-CoV-2 Delta or Omicron infection and performed SARS-CoV-2 viral load quantification, whole-genome sequencing, and variant-specific antibody characterization at the time of acute illness and convalescence. Viral load at the time of infection was inversely correlated with antibody binding and neutralizing antibody responses. Across all variants tested, convalescent neutralization titers in unvaccinated individuals were markedly lower than in vaccinated individuals. Increases in antibody titers and neutralizing activity occurred at convalescence in a variant-specific manner. For example, among individuals infected with the Delta variant, neutralizing antibody responses were weakest against BA.2, whereas infection with Omicron BA.1 variant generated a broader response against all tested variants, including BA.2.

High monkeypox vaccine acceptance among male users of smartphone-based online gay-dating apps in Europe, 30 July to 12 August 2022.

We assess monkeypox vaccination acceptance among male adults in the European Region. We conducted an online survey through two dating apps targeting men who have sex with men, from 30 July to 12 August 2022. We developed Bayesian hierarchical logistic regression models to investigate monkeypox vaccination acceptance. Overall crude vaccination acceptance was 82% and higher in north-western compared to south-eastern European regions. Acceptance strongly rose with perception of increased disease severity and transmission risk, and in individuals linked to healthcare.

Characteristics Associated With a Previous COVID-19 Diagnosis, Vaccine Uptake, and Intention to Be Vaccinated Among Essential Workers in the US Household Pulse Survey.

Objectives. To explore previous COVID-19 diagnosis and COVID-19 vaccination status among US essential worker groups. Methods. We analyzed the US Census Household Pulse Survey (May 26-July 5, 2021), a nationally representative sample of adults aged 18 years and older. We compared currently employed essential workers working outside the home with those working at home using adjusted prevalence ratios. We calculated proportion vaccinated and intention to be vaccinated, stratifying by essential worker and demographic groups for those who worked or volunteered outside the home since January 1, 2021. Results. The proportion of workers with previous COVID-19 diagnosis was highest among first responders (24.9%) working outside the home compared with workers who did not (13.3%). Workers in agriculture, forestry, fishing, and hunting had the lowest vaccination rates (67.5%) compared with all workers (77.8%). Those without health insurance were much less likely to be vaccinated across all worker groups. Conclusions. This study underscores the importance of improving surveillance to monitor COVID-19 and other infectious diseases among workers and identify and implement tailored risk mitigation strategies, including vaccination campaigns, for workplaces. (Am J Public Health. 2022;112(11):1599-1610. https://doi.org/10.2105/AJPH.2022.307010).

COVID-19 vaccine acceptance among medical students in Romania.

Vaccination against COVID-19 is a highly debated subject that brings confusion due to contradictory information coming from the scientific community and the media. Our aim was to focus on a homogeneous group of students in the healthcare field to assess their intention to vaccinate and the drivers behind this decision. A cross-sectional study was performed in the spring of 2021 in a Medical University in Romania. 725 of the undergraduates that completed an online questionnaire regarding their intention to vaccinate against COVID-19 were included in the study. Univariable analysis and logistic regression were performed on several variables to analyze factors affecting the willingness to vaccinate against COVID-19. In our study sample, 93.1% of students presented a strong intention to vaccinate, out of which the highest proportion belonged to subjects studying general medicine (96%). On logistic regression, we identified the following predictor factors: previous infection with coronavirus, prior vaccination refusal, VAX score, scientifically oriented sources of information and preference for RNA-based technology. Medical students have an increased willingness towards vaccination. Even for them, a highly educated and informed group of subjects, the general attitude towards vaccinations has a strong impact on the choice of COVID-19 vaccination.

[Expert recommendations on human papillomavirus vaccine immunization strategies in China].

HPV vaccination is the most effective way for preventing the cervical cancer. To respond the WHO calling for cervical cancer elimination, some Chinese provincial governments are launching the Free HPV Vaccination Programs for teenagers. Basing on the current stage of domestic utilization and the global immunization strategies of HPV vaccination, this paper provides a comprehensive review of the key aspects in the process of HPV vaccination, including subjects and priority vaccination population, vaccination dose and time interval, the principal of vaccination replacement, and the vaccination suggestion on special populations, etc. The article above contents and gives the advice on the immunization strategy of HPV vaccination in China.

Antibody and T-cellular response to COVID-19 booster vaccine in SARS-CoV-1 survivors.

The severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) survivors are more likely to produce a potent immune response to SARS-CoV-2 after booster vaccination. We assessed humoral and T cell responses against SARS-CoV-2 in previously vaccinated SARS-CoV-1 survivors and naïve healthy individuals (NHIs) after a booster Ad5-nCoV dose. Boosted SARS-CoV-1 survivors had a high neutralization of SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, and Delta but is limited to Omicron subvariants (BA.1, BA.2, BA.2.12.1, and BA.4/BA.5). Most boosted SARS-CoV-1 survivors had robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses. While booster vaccination in NHIs elicited less or ineffective neutralization of WA1, Beta, and Delta, and none of them induced neutralizing antibodies against Omicron subvariants. However, they developed comparable SARS-CoV-2-specific T cell responses compared to boosted SARS-CoV-1 survivors. These findings suggest that boosted Ad5-nCoV would not elicit effective neutralizing antibodies against Omicron subvariants in SARS-CoV-1 survivors and NHIs but induced comparable robust T cell responses. Achieving a high antibody titer in SARS-CoV-1 survivors and NHIs is desirable to generate broad neutralization.

Molecular epidemiology and clinical features of hand, foot and mouth disease requiring hospitalization after the use of enterovirus A71 inactivated vaccine in chengdu, China, 2017-2022: a descriptive study.

Three inactivated enterovirus A71 (EV-A71) vaccines have been widely vaccinated among children in the targeted age group in mainland China since mid-2016. However, comprehensive virological surveillance of hand, foot and mouth disease (HFMD) over multiple years after the use of EV-A71 vaccines has rarely been conducted. Using long-term data extracted from the Public Health and Clinical Center of Chengdu, we described the clinical, aetiological, and epidemiological characteristics of HFMD inpatients after the use of EV-A71 vaccines from 2017 through 2022. A total of 5115 patients were selected for analysis with a male-to-female ratio of 1.63:1 and were mostly under 5 years of age (97.6%). Among these cases, 4.3% presented with severe symptoms, and 4.1% of severe cases experienced significant complications. EV-A71 was no longer the major serotype for laboratory-confirmed HFMD, responsible for 15.6% of severe cases and 1.2% of mild cases. A significant downwards trend of EV-A71 infections was observed after the use of EV-A71 vaccines (P for trend < 0.001). Coxsackievirus A6 was the predominant pathogen, accounting for 63.5% of mild cases and 36.2% of severe cases. Coxsackievirus A10 (CV-A10) and A16 were sporadically detected, and an upwards trend was observed in the proportion of CV-A10 infections. This study provides baseline molecular epidemiology for the evaluation of EV-A71 vaccination impact and potential serotype replacement based on HFMD inpatients. Additional nationwide and population-based epidemiologic and serologic studies are essential to elucidate HFMD dynamics after the use of EV-A71 vaccines, and to inform public health authorities to introduce optimized intervention strategies.

Social expectations and government incentives in Malaysia's COVID-19 vaccine uptake.

High vaccination rates are integral to reducing infection and severity rates of COVID-19 infections within a community. We examine the role of social expectations in COVID-19 vaccination take-ups and its interaction with potential government actions in Malaysia. We find that individuals' expectations of others in their social groups towards vaccination predicts those individuals' vaccination registrations. Using a vignette experiment, we examine the extent of normative expectations in normalizing pro-vaccination behavior beyond an individual's reference group. We find that unless moderated by a high level of public trust, individuals prefer punitive policies as a way to increase vaccination rates in their communities.

Factors Associated with the Uptake of Antenatal Tetanus Toxoids Containing Vaccine by First-Time Mothers in Nigeria: Findings from the 2018 Nigerian Demographic Health Survey.

Background: Maternal and neonatal tetanus remains a public health problem in low-and-middle-income countries despite the increasing investment in tetanus toxoid containing vaccines (TTCV). Nigeria still records fatalities from tetanus, predominantly in women of reproductive age and in newborns. This is largely due to poor access to vaccinations and high rates of unsupervised labour and childbirth. We aim to investigate the antenatal uptake of TTCV and associated factors among first-time pregnant women in Nigeria. Methods: Data obtained from the 2018 Nigeria Demographic Health Survey (NDHS) was used to generate a list of eligible patients who in the last five years had undergone their first childbirth experience. Data was analysed using univariable and multivariable analyses and reported using a 95% confidence interval. Results: A total of 3640 participants were included in the analysis. 59.6% (95% CI, 57.6-61.8) of participants had received at least two doses of TTCV. Uptake of TTCV irrespective of current marital status was independently associated with number of and place of antenatal care. Other factors associated with receiving two doses of TTCV in all participants were ownership of mobile phones and region of residence. Among the currently married participants, wealth quintiles, region of residence, and having a polygamous family were additional associated factors. Conclusion: There was low uptake of the minimal required dosage of TTCV among first-time pregnant women with the lowest uptake in Northern regions relative to Southern regions. We recommend mixed methods studies to further explore the motivation behind TTCV uptake in pregnant women which can help guide future policies and interventions to improve uptake of tetanus immunization in Nigeria.

High Uptake and Series Completion of COVID-19 Vaccine at Community-Based Vaccination for Latinos With Limited English Proficiency.

BACKGROUND: Despite the disproportionate impact of COVID-19 on Latinos, there were disparities in vaccination, especially during the early phase of COVID-19 immunization rollout. METHODS: Leveraging a community-academic partnership established to expand access to SARS-CoV2 testing, we implemented community vaccination clinics with multifaceted outreach strategies and flexible appointments for limited English proficiency Latinos. RESULTS: Between February 26 and May 7 2021, 2250 individuals received the first dose of COVID-19 vaccination during 18 free community events. Among them, 92.4% (95% confidence interval [CI], 91.2%-93.4%) self-identified as Hispanic, 88.7% (95% CI, 87.2%-89.9%) were limited English proficiency Spanish speakers, 23.1% (95% CI, 20.9%-25.2%) reported prior COVID-19 infection, 19.4% (95% CI, 16.9%-22.25%) had a body mass index of more than 35, 35.0% (95% CI, 32.2%-37.8%) had cardiovascular disease, and 21.6% (95% CI, 19.2%-24.0%) had diabetes. The timely second-dose completion rate was high (98.7%; 95% CI, 97.6%-99.2%) and did not vary by outreach method. CONCLUSION: A free community-based vaccination initiative expanded access for Latinos with limited English proficiency at high risk for COVID-19 during the early phase of the immunization program in the US.

Risk of Guillain-Barré Syndrome Among Older Adults Receiving Influenza Vaccine in Taiwan.

Importance: Although influenza vaccination has been associated with Guillain-Barré syndrome (GBS), the findings among studies of older adult populations are inconsistent. Objective: To determine the risk of GBS after influenza vaccination among older adults. Design, Setting, and Participants: This cross-sectional study incorporated a self-controlled case series design. Days 1 to 7, days 1 to 14, and days 1 to 42 after influenza vaccination were identified as risk intervals; days 8 to 180, days 15 to 180, and days 43 to 180 comprised the corresponding control interval. Population-based data were obtained from Taiwan's National Health Insurance research database between January 1, 2003, and December 31, 2017. Data were analyzed from November 1, 2021, through February 28, 2022. Adults 65 years or older who developed GBS within 180 days after influenza vaccination were enrolled. Exposure: Government-funded seasonal influenza vaccination. Main Outcomes and Measures: Onset of GBS during risk intervals after influenza vaccination compared with control intervals using Poisson regression to calculate incidence rate ratio (IRR). Results: Of 13 482 122 adults aged 65 years or older who received an influenza vaccination, 374 were hospitalized for GBS. The mean (SD) age of the study population was 75.0 (6.1) years; 215 (57.5%) were men and 159 (42.5%) were women. In terms of comorbidities, 33 adults (8.8%) had cancer and 4 (1.1%) had autoimmune diseases. The IRRs for GBS during days 1 to 7, days 1 to 14, and days 1 to 42 were 0.95 (95% CI, 0.55-1.61; P = .84), 0.87 (95% CI, 0.58-1.29; P = .48), and 0.92 (95% CI, 0.72-1.17; P = .49), respectively. No results showed statistical significance. Similarly, no significant differences in IRRs were noted for the overall risk interval (ie, days 1-42) in subgroup analyses pertaining to different age groups (65-74 years [0.93 (95% CI, 0.66-1.31)], 75-84 years [0.85 (95% CI, 0.58-1.26)], and ≥85 years [1.10 (95% CI, 0.57-2.11)]), sex (men, 0.97 [95% CI, 0.71-1.33; P = .87]; women, 0.85 [95% CI, 0.58-1.23; P = .39]), Charlson Comorbidity Index (1.03 [95% CI, 0.77-1.38; P = .84]), or comorbidities (cancer, 0.68 [95% CI, 0.28-1.64; P = .39]; autoimmune disease, 1.10 [95% CI, 0.11-10.53; P = .94]). Conclusions and Relevance: These findings suggest that influenza vaccination did not increase the risk of GBS among adults aged 65 years or older in Taiwan regardless of postvaccination period or underlying characteristics.

Novel Vaccine Strategies and Factors to Consider in Addressing Health Disparities of HPV Infection and Cervical Cancer Development among Native American Women.

Cervical cancer is the 4th most common type of cancer in women world-wide. Many factors play a role in cervical cancer development/progression that include genetics, social behaviors, social determinants of health, and even the microbiome. The prevalence of HPV infections and cervical cancer is high and often understudied among Native American communities. While effective HPV vaccines exist, less than 60% of 13- to 17-year-olds in the general population are up to date on their HPV vaccination as of 2020. Vaccination rates are higher among Native American adolescents, approximately 85% for females and 60% for males in the same age group. Unfortunately, the burden of cervical cancer remains high in many Native American populations. In this paper, we will discuss HPV infection, vaccination and the cervicovaginal microbiome with a Native American perspective. We will also provide insight into new strategies for developing novel methods and therapeutics to prevent HPV infections and limit HPV persistence and progression to cervical cancer in all populations.

Cytomegalovirus-vaccine-induced unconventional T cell priming and control of SIV replication is conserved between primate species.

Strain 68-1 rhesus cytomegalovirus expressing simian immunodeficiency virus (SIV) antigens (RhCMV/SIV) primes MHC-E-restricted CD8+ T cells that control SIV replication in 50%-60% of the vaccinated rhesus macaques. Whether this unconventional SIV-specific immunity and protection is unique to rhesus macaques or RhCMV or is intrinsic to CMV remains unknown. Here, using cynomolgus CMV vectors expressing SIV antigens (CyCMV/SIV) and Mauritian cynomolgus macaques, we demonstrate that the induction of MHC-E-restricted CD8+ T cells requires matching CMV to its host species. RhCMV does not elicit MHC-E-restricted CD8+ T cells in cynomolgus macaques. However, cynomolgus macaques vaccinated with species-matched 68-1-like CyCMV/SIV mounted MHC-E-restricted CD8+ T cells, and half of the vaccinees stringently controlled SIV post-challenge. Protected animals manifested a vaccine-induced IL-15 transcriptomic signature that is associated with efficacy in rhesus macaques. These findings demonstrate that the ability of species-matched CMV vectors to elicit MHC-E-restricted CD8+ T cells that are required for anti-SIV efficacy is conserved in nonhuman primates, and these data support the development of HCMV/HIV for a prophylactic HIV vaccine.

The long term vaccine-induced anti-SARS-CoV-2 immune response is impaired in quantity and quality under TNFα blockade.

The humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients with chronic inflammatory disease (CID) declines more rapidly with tumor necrosis factor-α (TNF-α) inhibition. Furthermore, the efficacy of current vaccines against Omicron variants of concern (VOC) including BA.2 is limited. Alterations within immune cell populations, changes in IgG affinity, and the ability to neutralize a pre-VOC strain and the BA.2 virus were investigated in these at-risk patients. Serum levels of anti-SARS-CoV-2 IgG, IgG avidity, and neutralizing antibodies (NA) were determined in anti-TNF-α patients (n = 10) and controls (n = 24 healthy individuals; n = 12 patients under other disease-modifying antirheumatic drugs, oDMARD) before and after the second and third vaccination by ELISA, immunoblot and live virus neutralization assay. SARS-CoV-2-specific B- and T cell subsets were analysed by multicolor flow cytometry. Six months after the second vaccination, anti-SARS-CoV-2 IgG levels, IgG avidity and anti-pre-VOC NA titres were significantly reduced in anti-TNF-α recipients compared to controls (healthy individuals: avidity: p ≤ 0.0001; NA: p = 0.0347; oDMARDs: avidity: p = 0.0012; NA: p = 0.0293). The number of plasma cells was increased in anti-TNF-α patients (Healthy individuals: p = 0.0344; oDMARDs: p = 0.0254), while the absolute number of SARS-CoV-2-specific plasma cells 7 days after 2nd vaccination were comparable. Even after a third vaccination, these patients had lower anti-BA.2 NA titres compared to both other groups. We show a reduced SARS-CoV-2 neutralizing capacity in patients under TNF-α blockade. In this cohort, the plasma cell response appears to be less specific and shows stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were enhanced.