Dangers of mRNA vaccines

Abstract

“Necessity is the mother of invention:” An adage was brought to life with the emergence of the mRNA vaccine against the backdrop of the foreboding and mercurial COVID-19 pandemic. Considering a negligible adverse-effect profile and a break-neck manufacturing speed, it shone bright as the ideal vaccine candidate. However, “all that glitters is not gold,” as was evidenced by the significant reactogenicity, a host of multi-systemic side-effects, that are being reported by the vaccine recipients; which is palpably resulting in a shift of emotions for the vaccine, accounting for vaccine hesitancy. Anaphylaxis, antibody-dependent enhancements, and deaths, comprise the most serious side-effects, albeit occurring in sparing numbers. Storage and transportation require fastidious temperatures, rendering it substantially inaccessible to a country like India. The biggest jolt, however, was the unfolding of the biases in reporting vaccine efficacy, as only the attractively high numbers of the relatively equivocal relative risk reduction were reported while keeping at bay the meager numbers of the more forthright absolute risk reduction. Notwithstanding the fallacies, the mRNA vaccine still promises hope; and with the right precautions and finesse, can be potentiated, as “a watched pot never boils.”

Conscientious efforts to deter the proceedings of the COVID-19 pandemic are at present seeing 96 different types of vaccines under varying stages of development. Among these, two vaccines enjoying scrupulous attention are: BNT162b2 by Pfizer, Inc., and BioNTech, and mRNA-1273 by ModernaTX, Inc.; by virtue of belonging to a recently developed vaccine platform–the mRNA vaccine.[1]

An mRNA was utilized for therapeutic purposes first in 1989 when nanoparticles were successful in its in vitro transfection. Upon successful attainment of in vivo mRNA administration, the conception of its use as a vaccine soon ensued. Due to its efficacious immunological properties, remarkable safety and the advantage of malleability, it promised good candidature for a vaccine.[2] Under rigorous studying ever since, the need to bring it to the forefront arose with the onset of the SARS-CoV-2 triggered COVID-19 pandemic in December 2019.

The urgent tackling of the pandemic mandated development of a vaccine which would not only have a negligible adverse-effect profile, but also a breakneck speed of manufacturing. The mRNA vaccine fit the bill just right. The mRNA vaccine, instead of delivering a virus or a viral protein, would deliver genetic information, purporting the host's cells to produce the antigen–engendering the advantages of high biosafety and immune simulation without the risk of potential infection. Moreover, mRNA vaccine synthesis required only knowledge of the sequence coding for the desired immunogen, ensuring a fast paced production [Table 1].[3,4]

Table 1.

A brief description of the two messenger ribonucleic acid vaccines in current use, both eliciting similar humoral and cellular immune responses

	BNT162b2	mRNA-1273
General name	Pfizer/BioNTech vaccine	Moderna vaccine
FDA approval	December 11, 2020	December 18, 2020
Dosage	2 shots of 30 µg each, 21 days apart; given intramuscularly in deltoid muscle	2 shots of 50 µg each, 28 days apart; given intramuscularly in deltoid muscle
Age group	16 years and above	18 years and above
Effectiveness in preventing SARS-CoV-2 infection (%)	95	94.5
Cost	$19.8	$32-37

SARS-CoV-2 – Severe acute respiratory syndrome coronavirus 2; FDA – Food and drug administration; mRNA – Messenger ribonucleic acid

With the advent of the mRNA vaccines arose the inevitable concerns for its dangers. Without any eminent historic substantiation, its potential side-effects accounted for vaccine hesitancy in almost 50% of the population.[5] As per publications dating to the present day, both mRNA vaccines elicited similar and significant reactogenicity, when compared to placebo groups.[6]

These side effects mostly occur within 1–2 days of vaccination and are usually of mild to moderate intensity. Systemic effects are more commonly observed in younger age groups, owing to more robust immunities as compared to the elder age groups. Adverse effects usually last for 24–48 h before resolving on its own [Table 2].[6]

Table 2.

Reactogenicity of messenger ribonucleic acid vaccines

Symptoms	Frequency
Local symptoms (%)
Pain at injection-site	94.2
Swelling	15.05
Itching	14.58
Rash	13.43
Lymphadenopathy	4.17
Generalized symptoms (%)
Fatigue	65.74
Headache	59.26
Chills	52.78
Fever	35.65
Sweating	18.52
Dizziness	14.58
Musculoskeletal symptoms (%)
Myalgia	54.17
Arthralgia	24.77
Muscle stiffness	11.11
GI symptoms (%)
Nausea	26.62
Decreased appetite	13.19
Diarrhea	7.87
Abdominal pain	5.56
Heartburn	3.24
Vomiting	3.01
Psychiatric symptoms (%)
Decreased sleep	10.65
Anxiety	4.86
Depression	1.39
Eye and ENT (%)
Nasal stuffiness	6.48
Sore throat	6.02
Eye-pain	3.47
Coryza	2.78
Tinnitus	2.31
Endocrine symptoms (%)
Decreased appetite	13.19
Heat and cold intolerance	8.56
Increased thirst	3.24
Increased appetite	1.62
Increased urine	1.62
Respiratory symptoms (%)
Cough	3.47
Shortness of breath	2.31
CVS (%)
Palpitations	8.1
BP fluctuations	1.85
Syncope	0.93
Allergic (%)
Hives	1.62
Atopic eczema	0.93
Edema in face, lips and mouth	0.46
Anaphylaxis	0.23

GI – Gastrointestinal; ENT – Ear, nose, and throat; BP – Blood pressure; CVS – Cardio-vascular system

Anaphylaxis was reportedly seen in 2.5 cases per million doses administered, within 15 min in 90% of the cases; reaction being to the inactive ingredients or the excipients, and not the active ingredients.[6] Orofacial adverse effects such as edema of face, lips, tongue have been reported in 1:1000 cases. Facial edema was more commonly observed in those having dermatological fillers, and particularly with the Moderna Vaccine.[7] Bell's palsy was also reported, in a frequency 3.5–7 times higher than in the general population.[8]

Antibody-dependent enhancement resulting from mRNA vaccines has ensured the exclusion of immunocompromised patients and those on immunosuppressant therapies from vaccine trials. The neutralizing antibodies, resulting from vaccination, set off immunological cascades in the host, which may further deteriorate the general medical condition of the patient and also make easy the risk of viral infection in the patient. Infections being the most common cause of death in the immunocompromised, both variants of the mRNA vaccines are avoided in them.[3,9]

As per deaths being caused by these vaccines, reports are inscrutable and no conclusion can be derived, just as yet. However, studies and reports emerging from surveillance of hospitalized patients and elderly recipients suggest a mortality of 0.3%–0.5%. These numbers do not account for direct evidence, as the mortality rate in such cohorts is significant, notwithstanding.[10,11]

The mRNA vaccines present a potential disadvantage in terms of storage and transportation. Table 3 provides a look into the storage profile of the mRNA vaccines. The current need of the mRNA vaccines mandates manufacturing, shipping, and storing at large scales. The stringent conditions at which the vaccine remains stable thus hinders its global availability. Encountering the technical difficulties and overcoming the financial burden poses a particular challenge to low-income countries, like India, which already faces substantial energy crises.[3,12]

Table 3.

Storage profile of Pfizer/BioNTech vaccine and Moderna vaccine

Stability in	Frozen state	2-8°C (days)	Room temperature (h)
Pfizer/BioNTech vaccine	−80°C-−60°C, up to 6 months	5	2
Moderna vaccine	−25°C-−15°C	30	12

The efficacy of any vaccine is reported in terms of relative risk reduction (RRR) and absolute risk reduction (ARR). Relative risk is the ratio of attack rates with and without vaccination, which is 95% and 94.5% for Pfizer/BioNTech Vaccine and Moderna Vaccine, respectively.[4,1] However, measuring efficacy only by RRR introduces biases and foils the interpretation of vaccine-efficacy; it requires to be assessed in the setting of the risk of becoming infected with the SARS-CoV-2, which varies with time and populations under study, giving rise to the need for measurement of ARR. Absolute risk is the difference between attack-rates with vaccine and without vaccine, taking into purview the whole population at large. The ARR for Pfizer/BioNTech Vaccine is 0.7% and for Moderna Vaccine is 1.1%, both being meager values when compared to their enormous RRR counterparts. Medical and public health experts mandate the inclusion of both RRR and ARR to avoid outcome-reporting bias and a constructive conveyance of vaccine efficacy.[13] Authorities have decried the tendency to influence the people by presenting risk information using a relative risk approach, resulting in suboptimal decisions. It is therefore recommended to use an absolute risk format.[1] Notwithstanding the fallacies which emerge with the advent of the new-age mRNA vaccines, the hope it provides in overcoming a seemingly insurmountable and lethal pandemic largely eclipses most doubts about its credibility. All efforts should be made undertaken to vaccinate maximum number of people at the earliest.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.