Transient plasma viral rebound after SARS-CoV-2 vaccination in an exceptional HIV-1 elite controller woman.

BACKGROUND: Elite controllers are able to control viral replication without antiretroviral therapy. Exceptional elite controllers do not show disease progression for more than 25 years. Different mechanisms have been proposed and several elements of both innate and adaptive immunity are implicated. Vaccines are immune stimulating agents that can promote HIV-RNA transcription; transient plasma HIV-RNA detectability has been described within 7-14 days after different vaccinations. The most reliable mechanism involved in virosuppressed people living with HIV is a generalized inflammatory response that activates bystander cells harboring latent HIV. So far no data about viral load increase in elite controllers after SARS-CoV-2 vaccination are reported in literature. CASE PRESENTATION: We report the case of a 65-year-old woman of European ancestry, diagnosed with HIV-1/HCV co-infection more than 25 years ago. Since then, HIV-RNA remained undetectable and she never received ARV therapy. In 2021 she was vaccinated with mRNA-BNT162b2 vaccine (Pfizer-BioNTech®). She was administered with three doses in June, July and October 2021, respectively. The last available viral load was undetectable in March 2021. We observed an increase of VL at 32 cp/ml and 124 cp/mL, two and seven months after the second vaccine dose, respectively. During monthly follow-up, HIV-RNA gradually and spontaneously dropped becoming undetectable without ARV intervention. COVID-19 serology was positive with IgG 535 BAU/mL, showing response to vaccination. We measured total HIV-DNA at different time-points and we found it detectable both at the time of the higher plasma HIV-RNA (30 cp/10^6 PBMCs) and when it was undetectable (13 cp/10^6 PBMCs), in reduction. CONCLUSIONS: This case is the first report, to our knowledge, describing a rebound of plasma HIV-RNA in an elite controller after three doses of mRNA-BNT162b2 vaccine for SARS-CoV-2. Concomitantly with a spontaneous reduction of plasma HIV-RNA ten months after the third dose of mRNA-BNT162b2 vaccine (Pfizer-BioNTech®) without antiretroviral therapy intervention, we observed a reduction of total HIV-DNA in peripheral mononuclear cells. The potential role of vaccinations in altering HIV reservoir, even in elite controllers when plasma HIV-RNA is undetectable, could be a valuable aspect to take into account for the future HIV eradication interventions.

Persistent memory despite rapid contraction of circulating T Cell responses to SARS-CoV-2 mRNA vaccination.

Introduction: While antibodies raised by SARS-CoV-2 mRNA vaccines have had compromised efficacy to prevent breakthrough infections due to both limited durability and spike sequence variation, the vaccines have remained highly protective against severe illness. This protection is mediated through cellular immunity, particularly CD8+ T cells, and lasts at least a few months. Although several studies have documented rapidly waning levels of vaccine-elicited antibodies, the kinetics of T cell responses have not been well defined. Methods: Interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) were utilized to assess cellular immune responses (in isolated CD8+ T cells or whole peripheral blood mononuclear cells, PBMCs) to pooled peptides spanning spike. ELISA was performed to quantitate serum antibodies against the spike receptor binding domain (RBD). Results: In two persons receiving primary vaccination, tightly serially evaluated frequencies of anti-spike CD8+ T cells using ELISpot assays revealed strikingly short-lived responses, peaking after about 10 days and becoming undetectable by about 20 days after each dose. This pattern was also observed in cross-sectional analyses of persons after the first and second doses during primary vaccination with mRNA vaccines. In contrast, cross-sectional analysis of COVID-19-recovered persons using the same assay showed persisting responses in most persons through 45 days after symptom onset. Cross-sectional analysis using IFN-γ ICS of PBMCs from persons 13 to 235 days after mRNA vaccination also demonstrated undetectable CD8+ T cells against spike soon after vaccination, and extended the observation to include CD4+ T cells. However, ICS analyses of the same PBMCs after culturing with the mRNA-1273 vaccine in vitro showed CD4+ and CD8+ T cell responses that were readily detectable in most persons out to 235 days after vaccination. Discussion: Overall, we find that detection of spike-targeted responses from mRNA vaccines using typical IFN-γ assays is remarkably transient, which may be a function of the mRNA vaccine platform and an intrinsic property of the spike protein as an immune target. However, robust memory, as demonstrated by capacity for rapid expansion of T cells responding to spike, is maintained at least several months after vaccination. This is consistent with the clinical observation of vaccine protection from severe illness lasting months. The level of such memory responsiveness required for clinical protection remains to be defined.

Scientific Integrity Requires Publishing Rebuttals and Retracting Problematic Papers.

Recently, an article by Seneff et al. entitled "Innate immunosuppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs" was published in Food and Chemical Toxicology (FCT). Here, we describe why this article, which contains unsubstantiated claims and misunderstandings such as "billions of lives are potentially at risk" with COVID-19 mRNA vaccines, is problematic and should be retracted. We report here our request to the editor of FCT to have our rebuttal published, unfortunately rejected after three rounds of reviewing. Fighting the spread of false information requires enormous effort while receiving little or no credit for this necessary work, which often even ends up being threatened. This need for more scientific integrity is at the heart of our advocacy, and we call for large support, especially from editors and publishers, to fight more effectively against deadly disinformation.

Immunogenicity and Safety of Anti-SARS-CoV-2 mRNA Vaccines in a Cohort of Patients with Hereditary Angioedema.

Many factors may trigger hereditary angioedema (HAE) attacks. This study aims to gain insights into the benefits and potential risks of COVID-19 vaccination in HAE patients, focusing particularly on the possibility of triggering attacks. We enrolled 31 patients with HAE undergoing two doses of the SARS-CoV-2 mRNA Comirnaty-BioNTech/Pfizer vaccine. To evaluate the possible influence of the vaccine on disease control and attack frequency, we administered the angioedema control test (AECT) 4-week version before (T0), 21 days after the first dose (T1), and between 21 and 28 days after the second dose (T2). Despite 5 patients (16.1%) experiencing attacks within 72 h of the first dose administration, no significant variation in attack frequency was observed before and after vaccination [F(2,60) = 0.123; p = 0.799]. In addition, patients reported higher AECT scores at T1 and T2 compared to T0 [F(2,44) = 6.541; p < 0.05; post hoc p < 0.05)], indicating that the disease was rather more controlled after vaccinations than in the previous period. All patients showed a positive serological response to the vaccine without significant differences from healthy controls (U = 162; p = 0.062). These observations suggest that the vaccine administration is safe and effective in HAE patients.

Immunogenicity and Safety of mRNA Anti-SARS-CoV-2 Vaccines in Patients with Systemic Lupus Erythematosus.

Vaccination is the most effective preventive measure to control the spread of COVID-19 and reduce associated complications. This study aims to evaluate the efficacy and safety of mRNA COVID-19 vaccines in patients with systemic lupus erythematosus (SLE). A total of 41 adult SLE patients receiving two doses of the SARS-CoV-2 mRNA Comirnaty-BioNTech/Pfizer vaccine were enrolled. The quantitative determination of anti-trimeric spike protein-specific IgG antibodies to SARS-CoV-2 was assessed before (T0), 21 days after the administration of the first dose of the vaccine (T1), and between 21 and 28 days after the second dose (T2). They were compared with the same determinations from a cohort of 29 patients with C1-esterase inhibitor deficiency hereditary angioedema (C1-INH-HAE) as controls. All the SLE patients and controls demonstrated a positive serological response after a single dose of the vaccine (T1), which significantly increased after the second dose (T2). No significant difference was found between SLE patients and controls at T1 [t(52.81) = -0.68; p = 0.49] and at T2 [t(67.74) = -0.22; p = 0.825]. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) analysis showed that the vaccine did not influence SLE activity or caused disease flare in our cohort. In conclusion, COVID-19 vaccines produced a satisfactory response in SLE patients without variation in the disease activity.

Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs.

The mRNA SARS-CoV-2 vaccines were brought to market in response to the public health crises of Covid-19. The utilization of mRNA vaccines in the context of infectious disease has no precedent. The many alterations in the vaccine mRNA hide the mRNA from cellular defenses and promote a longer biological half-life and high production of spike protein. However, the immune response to the vaccine is very different from that to a SARS-CoV-2 infection. In this paper, we present evidence that vaccination induces a profound impairment in type I interferon signaling, which has diverse adverse consequences to human health. Immune cells that have taken up the vaccine nanoparticles release into circulation large numbers of exosomes containing spike protein along with critical microRNAs that induce a signaling response in recipient cells at distant sites. We also identify potential profound disturbances in regulatory control of protein synthesis and cancer surveillance. These disturbances potentially have a causal link to neurodegenerative disease, myocarditis, immune thrombocytopenia, Bell's palsy, liver disease, impaired adaptive immunity, impaired DNA damage response and tumorigenesis. We show evidence from the VAERS database supporting our hypothesis. We believe a comprehensive risk/benefit assessment of the mRNA vaccines questions them as positive contributors to public health.

De Novo Minimal Change Disease following Vaccination with the Pfizer/BioNTech SARS-CoV-2 Vaccine in a Living Kidney Donor.

Coronavirus disease 2019 has developed as a pandemic. Immunization with the introduction of vaccines against COVID-19 seems be the only way to end this pandemic. We report on a case of a kidney donor, who developed minimal change disease (MCD) within 4 days post-vaccination with the SARS-CoV-2 BNT162b2 mRNA vaccine (Pfizer/BioNTech). She donated her kidney to her husband 4 years ago. After receiving the 1st vaccine dose, she presented with nephrotic syndrome, with complete remission 5 days later. She proceeded with the second dose of the BNT162b2 vaccine at the appointed time. Two days later, she presented with a relapse of full-blown nephrotic syndrome with preserved renal function. We performed an ultrasound-guided percutaneous kidney biopsy and the final diagnosis was consistent with minimal change disease. Oral prednisolone was promptly initiated at a dosage of 1 mg/kg daily and complete remission was achieved 10 days later. More data about this rare appearance of de novo glomerular diseases after SARS-CoV-2 vaccination are emerging and should be interpreted rigorously.

mRNA COVID-19 Vaccines and Long-Lived Plasma Cells: A Complicated Relationship.

mRNA COVID-19 vaccines have hegemonized the world market, and their administration to the population promises to stop the pandemic. However, the waning of the humoral immune response, which does not seem to last so many months after the completion of the vaccination program, has led us to study the molecular immunological mechanisms of waning immunity in the case of mRNA COVID-19 vaccines. We consulted the published scientific literature and from the few articles we found, we were convinced that there is an immunological memory problem after vaccination. Although mRNA vaccines have been demonstrated to induce antigen-specific memory B cells (MBCs) in the human population, there is no evidence that these vaccines induce the production of long-lived plasma cells (LLPCs), in a SARS-CoV-2 virus naïve population. This obstacle, in our point of view, is caused by the presence, in almost all subjects, of a cellular T and B cross-reactive memory produced during past exposures to the common cold coronaviruses. Due to this interference, it is difficult for a vaccination with the Spike protein alone, without adjuvants capable of prolonging the late phase of the generation of the immunological memory, to be able to determine the production of protective LLPCs. This would explain the possibility of previously and completely vaccinated subjects to become infected, already 4-6 months after the completion of the vaccination cycle.

Anti-SARS-CoV-2 mRNA vaccines as inducers of humoral response against apolipoprotein A-1?

BACKGROUND: COVID-19 and some anti-SARS-CoV-2 vaccines trigger a humoral autoimmune response against a broad range of endogenous components, which may affect recipients' prognosis in predisposed individuals. Autoantibodies directed against apolipoprotein A-1 (AAA1 IgG) the major protein fraction of High Density Lipoprotein have been shown to be raised in COVID-19 and in rheumatoid arthritis (RA) patients and other populations where they have been associated with poorer outcomes. We wanted to assess the impact of anti-SARS-CoV-2 mRNA-based vaccination on AAA1 autoimmune biomarkers in RA patients. METHODS: 20 healthy controls and 77 RA mRNA-based vaccinated patients were collected at baseline, 3 weeks after the first vaccination, 2 and 8 weeks after the second vaccination. AAA1 and SARS-CoV-2 serologies were measured by immunoassays. Systemic and local symptoms occurring during the vaccination protocol were recorded. RESULTS: mRNA-based vaccination induced a significant increase in median AAA1 IgG levels in both healthy controls and RA patients overtime. However, in both populations, these medians trend did not translate into significant increase in AAA1 IgG seropositivity rates despite evolving from 5 to 10% in healthy controls, and from 9 to 12.9% in RA patients. No associations were retrieved between AAA1 IgG and symptoms of any kind during the vaccination protocol. CONCLUSIONS: mRNA-based vaccination seems to induce a light AAA1 IgG response in immunocompetent individuals within 2 months after the last injection. Although we did not observe any warning signs, the formal demonstration of the harmlessness of such biological warrants further studies.

Adverse events following mRNA SARS-CoV-2 vaccination among U.S. nursing home residents.

BACKGROUND: The devastating impact of the SARS-CoV-2 pandemic prompted the development and emergency use authorization of two mRNA vaccines in early 2020. Vaccine trials excluded nursing home (NH) residents, limiting adverse event data that directly apply to this population. METHODS: To prospectively monitor for potential adverse events associated with vaccination, we used Electronic Health Record (EHR) data from Genesis HealthCare, the largest NH provider in the United States. EHR data on vaccinations and pre-specified adverse events were updated daily and monitored for signal detection among residents of 147 facilities who received the first dose of vaccine between December 18, 2020 and January 3, 2021. For comparison, unvaccinated residents during the same time period were included from 137 facilities that started vaccinating at least 15 days after the vaccinating-facilities. RESULTS: As of January 3, 2021, 8553 NH residents had received one dose of SARS-CoV-2 vaccine and by February 20, 2021, 8371 residents had received their second dose of vaccine; 11,072 were included in the unvaccinated comparator group. No significant associations were noted for neurologic outcomes, anaphylaxis, or cardiac events. CONCLUSIONS: No major safety problems were detected following the first or second dose of the vaccine to prevent COVID-19 in the study cohort from December 18, 2020 through March 7, 2021.