SARS-CoV-2 vaccines: Lights and shadows

Abstract

Vaccines to prevent acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicit an immune neutralizing response. Some concerns have been raised regarding the safety of SARS-CoV-2 vaccines, largely based on case-reports of serious thromboembolic events after vaccination. Some mechanisms have been suggested which might explain the adverse cardiovascular reactions to SARS-CoV-2 vaccines. Different vaccine platforms are currently available which include live attenuated vaccines, inactivated vaccines, recombinant protein vaccines, vector vaccines, DNA vaccines and RNA vaccines. Most vaccines increase the endogenous synthesis of SARS-CoV-2 Spike proteins from a variety of cells. Once synthetized, the Spike proteins assembled in the cytoplasma migrate to the cell surface and protrude with a native-like conformation. These proteins are recognized by the immune system which rapidly develops an immune response. Such response appears to be quite vigorous in the presence of DNA vaccines which encode viral vectors, as well as in subjects who are immunized because of previous exposure to SARS-CoV-2. The resulting pathological features may resemble those of active coronavirus disease. The free-floating Spike proteins synthetized by cells targeted by vaccine and destroyed by the immune response circulate in the blood and systematically interact with angiotensin converting enzyme 2 (ACE2) receptors expressed by a variety of cells including platelets, thereby promoting ACE2 internalization and degradation. These reactions may ultimately lead to platelet aggregation, thrombosis and inflammation mediated by several mechanisms including platelet ACE2 receptors. Whereas Phase III vaccine trials generally excluded participants with previous immunization, vaccination of huge populations in the real life will inevitably include individuals with preexisting immunity. This might lead to excessively enhanced inflammatory and thrombotic reactions in occasional subjects. Further research is urgently needed in this area.

Gender Specific Differences in Disease Susceptibility: The Role of Epigenetics

“…Even if, to date, no extensive studies have been published on the possible gender bias regarding the efficacy and any adverse reactions to vaccines against SARS-CoV-2 infection, some recent reports indicate that certain vaccines (ChAdOx1 nCoV-19 and the Ad26.COV2. S, which are both DNA-vectored vaccines against SARS-CoV-2 infection) can induce a rare clinical syndrome characterized by thrombosis at atypical sites combined with thrombocytopenia, occurring within 2 weeks of vaccination in women under 60 years of age, with lethality due to thrombosis in a minority of them [196][197][198].…”

Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update

“…Vaxzevria updated its data analysis of its phase 3 trials in March 2021, showing its vaccine to be 76% effective at reducing the risk of symptomatic disease 15 days or more after receiving the two doses, and 100% against severe disease. The company also said the vaccine was 85% effective in preventing COVID-19 in people over 65 ( 237 ).…”

“…It can be used much more extensively than mRNA vaccinations because it only has to be refrigerated rather than frozen. However, Vaxzevria trajectory has been tumultuous, jolted by conflicting messages from AstraZeneca, high-profile safety concerns, and manufacturing difficulties ( 237 ). In April 2021, the European Medicines Agency’s (EMA) protection committee concluded that “unusual blood clots and reduced blood platelets should be identified as extremely unlikely side effects” that could occur within two weeks of vaccination.…”

“…The vaccine showed 72% overall efficacy and 86% efficacy against severe disease in the U.S. The protection starts around 14 days after vaccination but it is not known how long protection continues ( 237 , 238 ). In contrast to the Pfizer and Moderna vaccines, this vaccine is easier to store and only includes a single dose, which simplifies distribution and administration.…”

Coronavirus Disease-19 Vaccines Best Reflect Effective Pharmaceuticals

“…It has been recently suggested that the SARS-CoV-2 S protein produced and released by the host cells previously targeted by vaccines may interact with its ACE2 receptor expressed on other cells, trigger inflammation, thrombosis, and other adverse reactions, eventually mimicking disease pathology (Angeli et al 2021). Would this be the case, then such unintended consequences of vaccine-induced S protein production could depend on the cells, tissues and organs where production occurs; the amount of protein produced and released; and the time-course of its production and release.…”