Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis.

The emergence of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with decreased susceptibility to neutralization has generated interest in assessments of booster doses and variant-specific vaccines. Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study ( NCT04405076 ) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273.211. As the trial is currently ongoing, this exploratory interim analysis includes preliminary descriptive results only of four booster groups (n = 20 per group). Immediately before the booster dose, neutralizing antibodies against wild-type D614G virus had waned (P < 0.0001) relative to peak titers against wild-type D614G measured 1 month after the primary series, and neutralization titers against B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) VOCs were either low or undetectable. Both the mRNA-1273 booster and variant-modified boosters were safe and well-tolerated. All boosters, including mRNA-1273, numerically increased neutralization titers against the wild-type D614G virus compared to peak titers against wild-type D614G measured 1 month after the primary series; significant increases were observed for mRNA-1273 and mRNA-1273.211 (P < 0.0001). In addition, all boosters increased neutralization titers against key VOCs and VOIs, including B.1.351, P.1. and B.1.617.2, that were statistically equivalent to peak titers measured after the primary vaccine series against wild-type D614G virus, with superior titers against some VOIs. This trial is ongoing.

Side effects of BNT162b2 mRNA COVID-19 vaccine: A randomized, cross-sectional study with detailed self-reported symptoms from healthcare workers.

INTRODUCTION: Concerns are prevailing about the safety and side effects of the BNT162b2 mRNA vaccine for coronavirus disease 2019 (COVID-19). METHODS: A randomized, cross-sectional study was performed to investigate the side effects of the BNT162b2 vaccine using an independent online questionnaire gathering responses from healthcare workers (HCWs) with detailed review of organ systems. RESULTS: Of all HCWs, 87.98% (1245/1415) completed the survey. Of them, 64.5% (803/1245) received the BNT162b2 mRNA vaccine and reported at least one or more symptoms (classified based on organ systems and occurrence rate) post vaccination. Of these, 640/803 (79.7%) were able to continue activities of daily living (ADL), 103/803 (12.83%) had trouble temporarily to perform ADL, 99/803 (12.33%) took time off work temporarily, 20/803 (2.49%) required help from an outpatient provider, 5/803 (0.62%) required help from an emergency department and 2/803 (0.25%) required hospitalization. Despite this, 97.61% intended to have the second dose and 92.9% had already received it. CONCLUSIONS: Commonly reported symptoms (occurrence in descending order) were soreness, fatigue, myalgia, headache, chills, fever, joint pain, nausea, muscle spasm, sweating, dizziness, flushing, feelings of relief, brain fogging, anorexia, localized swelling, decreased sleep quality, itching, tingling, diarrhoea, nasal stuffiness and palpitations. Despite this, remarkable acceptance for the second dose of the BNT162b2 vaccine was found among HCWs.

Implications of mRNA-based SARS-CoV-2 vaccination for cancer patients.

SARS-CoV-2 infection and the resulting COVID-19 have afflicted millions of people in an ongoing worldwide pandemic. Safe and effective vaccination is needed urgently to protect not only the general population but also vulnerable subjects such as patients with cancer. Currently approved mRNA-based SARS-CoV-2 vaccines seem suitable for patients with cancer based on their mode of action, efficacy, and favorable safety profile reported in the general population. Here, we provide an overview of mRNA-based vaccines including their safety and efficacy. Extrapolating from insights gained from a different preventable viral infection, we review existing data on immunity against influenza A and B vaccines in patients with cancer. Finally, we discuss COVID-19 vaccination in light of the challenges specific to patients with cancer, such as factors that may hinder protective SARS-CoV-2 immune responses in the context of compromised immunity and the use of immune-suppressive or immune-modulating drugs.

Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent.

Vaccines and therapeutics using in vitro transcribed mRNA hold enormous potential for human and veterinary medicine. Transfection agents are widely considered to be necessary to protect mRNA and enhance transfection, but they add expense and raise concerns regarding quality control and safety. We found that such complex mRNA delivery systems can be avoided when transfecting epithelial cells by aerosolizing the mRNA into micron-sized droplets. In an equine in vivo model, we demonstrated that the translation of mRNA into a functional protein did not depend on the addition of a polyethylenimine (PEI)-derived transfection agent. We were able to safely and effectively transfect the bronchial epithelium of foals using naked mRNA (i.e., mRNA formulated in a sodium citrate buffer without a delivery vehicle). Endoscopic examination of the bronchial tree and histology of mucosal biopsies indicated no gross or microscopic adverse effects of the transfection. Our data suggest that mRNA administered by an atomization device eliminates the need for chemical transfection agents, which can reduce the cost and the safety risks of delivering mRNA to the respiratory tract of animals and humans.

COVID-19 Vaccine Concerns: Fact or Fiction?

One year has elapsed since a team of Chinese scientists reported the first case of COVID-19 in Wuhan, China on January 8, 2020, after sequencing the first viral genetic material. Since then, many vaccines were rushed into testing, bypassing animal experimentations, with more than 200 pharma companies in different countries declaring the development of different vaccines, each with their own strategy for generating immunity, despite the arguments of many infectious disease experts that 18 months for a first vaccine is an incredibly aggressive schedule because it takes an average of 10 years to develop a vaccine. Ten vaccine candidates have already entered phase 3 clinical trials in humans. These vaccines rely on different types of technology, the most innovative of which use the genetic material messenger RNA. Many provocative questions and genuine concerns have been raised, such as short durations of efficacy and safety follow-ups, lack of identified correlates of protection, morbidity and mortality cases reported shortly after vaccination, uncertainties regarding the risk of enhanced disease on exposure to the virus in the long-term, the possibility of viral transmission after vaccination, the reported reduced efficacies of these vaccines against new variants, the efficacy and safety of these vaccines in the previously excluded subgroups (such as children, pregnant women, the frail elderly high-risk population, and immunocompromised individuals), the unknown risk of immunogenicity-induced autoimmune diseases, cancer and chronic inflammation, the risk of genome transformation (mainly in the presence of reverse transcriptase), and finally the potential coercion that may be imposed by either public or private sectors on citizens to receive the vaccine. Many plausible questions are apparent, with no clear and convincing answers.

Potential mechanisms of anaphylaxis to COVID-19 mRNA vaccines.

Anaphylaxis to vaccines is historically a rare event. The coronavirus disease 2019 pandemic drove the need for rapid vaccine production applying a novel antigen delivery system: messenger RNA vaccines packaged in lipid nanoparticles. Unexpectedly, public vaccine administration led to a small number of severe allergic reactions, with resultant substantial public concern, especially within atopic individuals. We reviewed the constituents of the messenger RNA lipid nanoparticle vaccine and considered several contributors to these reactions: (1) contact system activation by nucleic acid, (2) complement recognition of the vaccine-activating allergic effector cells, (3) preexisting antibody recognition of polyethylene glycol, a lipid nanoparticle surface hydrophilic polymer, and (4) direct mast cell activation, coupled with potential genetic or environmental predispositions to hypersensitivity. Unfortunately, measurement of anti-polyethylene glycol antibodies in vitro is not clinically available, and the predictive value of skin testing to polyethylene glycol components as a coronavirus disease 2019 messenger RNA vaccine-specific anaphylaxis marker is unknown. Even less is known regarding the applicability of vaccine use for testing (in vitro/vivo) to ascertain pathogenesis or predict reactivity risk. Expedient and thorough research-based evaluation of patients who have suffered anaphylactic vaccine reactions and prospective clinical trials in putative at-risk individuals are needed to address these concerns during a public health crisis.