COVID mRNA Vaccines Cause Persistent Inflammation

Journal of Clinical Investigation, 2023

Vaccines

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 ...

2021

We present a comprehensive analysis of antibody and cellular responses in children aged 12-16 years who received COVID-19 vaccination with ChAdOx1 (n=6) or mRNA vaccine (mRNA-1273 or BNT162b2, n=9) using a 12-week extended-interval schedule. mRNA vaccination of seropositive children induces high antibody levels, with one dose, but a second dose is required in infection-naïve children. Following a second ChAdOx1 dose, antibody titres were higher than natural infection, but lower than mRNA vaccination. Vaccination induced live virus neutralising antibodies against Alpha, Beta and Delta variants, however, a second dose is required in infection-naïve children. We found higher T-cell responses following mRNA vaccination than ChAdOx1. Phenotyping of responses showed predominantly early effector-memory CD4 T cell populations, with a type-1 cytotoxic cytokine signature, with IL-10. These data demonstrate mRNA vaccination induces a co-ordinated superior antibody and robust cellular responses...

Science Advances

Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high–temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of int...

Cell Discovery, 2021

Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8+ T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infectio...

Vaccines

Twenty individuals (17 females, 3 males, aged 31–65 years (range), median: 46) who received both doses of the BioNTech Pfizer mRNA vaccine were examined (11 to 31 days, median: 25) after the second dose for the presence of antibodies against peptides of SARS-COV-2 and some of MERS-CoV, SARS-CoV1, HCov229E, and HCoVNL63. Clinical evaluation revealed that six people had COVID-19 in the past. We found that: (i) Six people claimed the presence of unwanted effects of vaccination, which were more frequent in those with a history of COVID-19 (4 out of 6 vs. 2 out of 14, p = 0.037); (ii) All individuals independent of the past history of COVID-19 responded equally well in IgG but those who experienced the disease tended to do better in IgA class (729.04 vs. 529.78 U/mL, p = 0.079); (iii) All those who had experienced the disease had IgG antibodies against nucleocapsid antigens but also 5 out of 14 who had not had the disease (6/6 vs. 5/14, p = 0.014); (iv) Anti S2 antibodies were present in...

Journal of obstetrics, gynecology and cancer research, 2023

The COVID-19 pandemic has disrupted people's lives all over the world, and vaccination is one of the best ways to eradicate this pandemic and save people's lives. Despite this, vaccines have many known and unknown side effects like fever, fatigue, headache, etc. Fertility is an important aspect of human life, but there are too many concerns about its relationship with COVID-19 and its vaccines. Women are complaining of menstrual irregularities like postmenopausal bleeding, heavy menstrual bleeding, polymenorrhea and fertility concerns after receiving the second dose of the COVID-19 vaccine. The immunologic reactions between vaccine ingredients and the immune system of the body seem to be responsible for this global issue. Angiotensinconverting enzyme 2 (ACE2) and Basigin (BSG) are the receptors for SARS-COV-2. ACE2 is expressed in the human respiratory system, kidney, vagina, uterus and particularly widely in the ovaries, and BSG is expressed in the uterus, ovary stroma and granulosa cells. Therefore, SARS-COV-2 can invade the target cells by attachment to ACE2 and BSG and modulate their expression, and through these probable mechanisms, it can disturb female reproduction and menstruation. According to this accumulated evidence, in this study we aimed at summarizing the recent studies with a focus on probable mechanisms by which SARS-COV-2 and COVID-19 vaccines affect menstruation irregularities and reproduction complications.

Journal of Controlled Release, 2021

In less than one year since the outbreak of the COVID-19 pandemic, two mRNA-based vaccines, BNT162b2 and mRNA-1273, were granted the first historic authorization for emergency use, while another mRNA vaccine, CVnCoV, progressed to phase 3 clinical testing. The COVID-19 mRNA vaccines represent a new class of vaccine products, which consist of synthetic mRNA strands encoding the SARS-CoV-2 Spike glycoprotein, packaged in lipid nanoparticles to deliver mRNA to cells. This review digs deeper into the scientific breakthroughs of the last decades that laid the foundations for the rapid rise of mRNA vaccines during the COVID-19 pandemic. As well as providing momentum for mRNA vaccines, SARS-CoV-2 represents an ideal case study allowing to compare design-activity differences between the different mRNA vaccine candidates. Therefore, a detailed overview of the composition and (pre)clinical performance of the three most advanced mRNA vaccines is provided and the influence of choices in their structural design on to their immunogenicity and reactogenicity profile is discussed in depth. In addition to the new fundamental insights in the mRNA vaccines' mode of action highlighted here, we also point out which unknowns remain that require further investigation and possibly, optimization in future mRNA vaccine development. COVID-19 creates momentum for mRNA vaccines Since Edward Jenner's fist successful vaccination studies in the late 1700's, vaccine development and large-scale immunization campaigns have been society's response to infectious disease outbreaks worldwide. The COVID-19 pandemic is in that sense no different, although it is remarkable that the global search for a vaccine against SARS-CoV-2 has introduced a completely new class of vaccine products: at least three of the candidates that are in the forefront of the vaccine development race are messenger RNA (mRNA) nanoparticles. This is quite a revolution in vaccinology. To exemplify, all of the basal vaccines recommended by the World Health Organization (WHO) trigger immunity by injecting weakened or whole inactivated pathogens. The more recently developed vaccines, such as the ones against the human papillomavirus (HPV), Hepatitis B or the seasonal flu no longer contain intact virus particles, but rather purified or recombinantly produced viral proteins, which need to be delivered in combination with immune adjuvants to improve the vaccine's immunogenicity. The mRNA vaccines for COVID-19 do not resemble any of these vaccine products whatsoever, as they do not contain protein compounds, let alone whole virus particles. By contrast, they consist of mRNA strands packaged in a

Journal of Pharmaceutical Research International

Coronavirus disease-2019 (COVID-19) is an outbreak on a scale unseen in modern human history. More than two years after the outbreak began, there are 271 million fatalities and more than 5.32 million mortalities reported globally. Vaccination has been the most successful medical intervention in the last century to minimize mortality and suffering due to infectious illnesses. Only the discovery and dissemination of an effective vaccine will probably result at the end of this pandemic. Tremendous attempts have also been made to develop secure and convenient vaccinations. Vaccination is an efficient method of preventing viral illness, stopping its spread, and developing protective immunity. Improved understanding of protective immunity and significant advances in gene editing has enabled the development of a wide range of novel vaccines by manipulating sugars, RNA, proteins, and DNA. The development of attenuated mutants, the expression of prospective antigens in live vectors, and the ...

Journal of Clinical Investigation, 2023

BACKGROUND. Maintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown. METHODS. We measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses. RESULTS. The booster (third immunization) dose at 6 to 10 months increased the half-life of the serum-neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months. CONCLUSION. The durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.