|Year : 2020 | Volume
| Issue : 2 | Page : 21-24
SARS-CoV-2 vaccines: A brief review
Brandon Chatani1, Daniel K Ng2
1 Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA
2 Department of Paediatrics, Hong Kong Sanatorium & Hospital, Hong Kong, China
|Date of Submission||19-Jan-2021|
|Date of Acceptance||20-Jan-2021|
|Date of Web Publication||09-Mar-2021|
Assistant Professor of the Department of Pediatrics, Division of Pediatric Infectious Diseases, Associate Program Director of the Pediatric Infectious Disease Fellowship, University of Miami Miller School of Medicine, Miami, Florida
Source of Support: None, Conflict of Interest: None
SARS-CoV-2 has immensely changed the landscape in how vaccines are researched and developed. The timeline truncated for the propose of meeting the grave demand. Children stand to benefit from herd immunity for multiple reasons. Protection from SARS-CoV-2 would not only protect children from COVID but also a unique entity called Multisystem Inflammatory Syndrome in Children (MISC). Thus, it is vital that general pediatricians and practitioners who care for children to have foundational knowledge regarding the ever-expanding array of soon to be available COVID19 vaccines along with the potential pitfalls of their rushed development and implementation. This article seeks to provide a brief review of the most prominent COVID19 vaccines under development with intention for Pediatric use as well as recall historical knowledge regarding rushed development of respiratory viral vaccines that resulted in unintended consequences.
Keywords: SARS-CoV-2, Vaccine, COVID, Pediatric, Corona virus, RSV
|How to cite this article:|
Chatani B, Ng DK. SARS-CoV-2 vaccines: A brief review. Pediatr Respirol Crit Care Med 2020;4:21-4
| Introduction|| |
The climate of the COVID19 Pandemic has put vaccine development to rush order. Several manufacturers moved products through early research and development at outstanding paces. By early August 2020, there were at least eight vaccines in large-scale efficacy tests, primarily focused on the adult population. From the laboratory to clinic, a vaccine passes through several trials to become approved and available for commercial use. The start for COVID19 was in January 2020, virologist sought to decode the genomic contents of the virus. By identifying the bevy of possible antigen targets, trials could begin to test which would elicit an immune response. The production of antibodies isn't enough, the antibodies which the host produces must have an activity to prevent infection. Animal testing is moved to human testing in small groups, then larger groups to ensure safety of proposed vaccine products. The greatest hurdle then is being the large-scale efficacy trials which would need to show that the vaccine provides protection to at least 50% of vaccinated people to be approved by agencies such as the United States Federal Drug Administration (FDA) and the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom.
| Vaccines|| |
Companies such as ModernaTX, Inc. and Pfizer, Inc. own some of the vaccine products that have passed through Phase 3 trials, as seen on ClinicalTrials.gov. They have chosen products based on nucleoside-modified messenger RNA (mRNA). Their teams identified mRNA in COVID19 which could be modified to allow perfusion into the human body and instigate an immunologic response. The sites for targeting antibodies against the virus can vary, however, the large majority of vaccine products under investigation, the site of focus is a protein on the viral envelope (spike protein). As of December 2, 2020, both the FDA and the MHRA have approved the product developed by Pfizer/BioNTech. The two regulatory agencies conducted independent reviews of data from the laboratory pre-clinical studies, clinical trials, and manufacturing quality controls, in addition to their own laboratory testing of the product to ensure stringent safety and quality standards are met in every batch. Both regulatory agencies are globally recognized for their mechanisms by which safety and efficacy of vaccine products are ensured. It is certainly no small feat to gain approval from both in the time which it was achieved.
In a different approach, Sinovac Biotech Ltd. produced a vaccine by a more traditional route via an inactivated viral strain, similar to the way the inactivate poliovirus vaccine was produced. Although in this case, the vaccine involves the CN2 strain of SARS-Cov2 isolated from a COVID19 positive patient, augmented in cell culture, and inactivated by beta-propiolactone.
Yet, another approach to confer immunity to COVID19 with a vectored vaccine which has gained much attention is truly on the cutting edge of science and modern medicine. Few manufacturers based their vaccine on vectored delivery of the immunogenic vaccine components via a recombinant adenovirus. A few of the companies that have utilized a vector-based vaccine approach include CanSino Biological/Beijing Institute of Biotechnology (China), Johnson and Johnson (USA), and AstraZeneca (UK). From a publication on September 4, 2020, the results from Logunov et al. indicate a promising candidate from Russia, vaccine rAd26-S and rAd5-S. This heterologous COVID-19 vaccine utilizes two-recombinant adenoviral vectors (type 26 and type 5) to carry the gene for SARS-CoV-2 spike glycoprotein. Investigators studied the system as a two-dose series at day 0 and day 28. They identified a reported 100% seroconversion rate after the second dose with the most common adverse events not unlike the other vaccine trials currently ongoing, including pain at the injection site, hyperthermia, headache, asthenia, and muscle and joint pain. Of note, the preliminary results published in Lancet include a very small sample size of 38 volunteers. The majority of volunteers were white males, who were confirmed seronegative for SARS-CoV-2 and of normal height and weight. Although a high serologic conversion rate is published in their findings, there remains the question of efficacy to prevent infection. Similarly, there are preliminary results for the product of AstraZeneca which are comparable to the Logunov et al. A unique finding found among recipients of AZD1222 was decreased adverse events among individuals older than 56 years old. The adenoviral components of the vaccine may prompt an immune response targeting adenovirus types 26 and 5, rather than the COVID19 spike protein. It is too soon to tell in what ways this will alter the efficacy of the cellular and humoral responses, whether to produce an efficacious mode of prevention or possibly deleterious mode of promotion. An overview comparing each of the aforementioned vaccines is provided in [Figure 1]. Whether based on an inactivated viral strain or a modified mRNA or viral-based vector, each approach has benefits and risks associated with administration into the human body that only further study and careful analysis will discover.
| Considerations for Pediatric Population|| |
A special population to consider in the administration and utilization of vaccines is the pediatric population. Initial vaccine approvals have been for young adults and older; for example, Pfizer's vaccine has been authorized for ages 16 and up, while Moderna's vaccine is currently authorized for ages 19 and up. Both have ongoing trials for younger children as young as 12 years old. This age group is of particular interest because of the known increased rate of transmission and disease severity found among them. Bunyavanich et al. first described the possible link between angiotensin-converting enzyme 2 in the nasal epithelium as a mode by which the attenuation of transmission and disease occurs with younger ages. Of the 305 individuals tested, aged 4 years to 60 years, there was a logarithmic correlation of age with the quantity of ACE2 gene expression in the nasal epithelium. In each age bracket, <10 years old, 10–17 years, 18–24 years, and >25 years old, there was an increase in present ACE2 found to be statistically significant (P = 0.1, <0.001, =0.001, respectively). The role of ACE2 in SARS-CoV-2 host entry is a major difference compared to SARS-CoV-1, which augments its ability to transmit from one human to another in the pandemic. Within the USA, the return to in-person school was met with many outbreaks, especially among the 12–18-year-old population. From March to September of 2020, the Centers for Disease Control and Prevention in the USA noted among adolescents aged 12–17 years, the number of COVID19 cases was twice the amount compared to children aged 5–11 years old. Pediatric advocacy groups should urge for teachers and adolescents who qualify for the vaccine to be placed on the priority list for public safety. As for the younger aged children, more time will be necessary for appropriate testing to validate safety and efficacy.
| Potential Pitfalls|| |
Although the call to control COVID19 has been powerful, it could potentially lure investigators and clinicians to rushing to a product that does more harm than good. The ultimate benefit of administrating a vaccine is the stimulation of neutralizing antibodies which protect the individual from developing disease after exposure to the virus. However, the level of this benefit of immune protection is limited by a variety of factors, such as the level of response, type of response, and sustainability of response. Respiratory syncytial virus (RSV) provides us with a historical background for previous pitfalls and limitations of vaccines targeting respiratory viruses. From autoimmune disease to variable immune response, the legacy of RSV immunization tests dating from the 1960s outlines possibilities which may be seen on the path to eradicating COVID19. In some cases, RSV vaccines elicited a hyperimmune response at the time of natural infection causing more severe disease. In the initial trials, almost 80% of the formalin-inactivated RSV vaccine recipients required hospitalization and a handful died., Already, some research trials identify COVID19 vaccines resulting in an increased eosinophilic proinflammatory pulmonary response. Dengue virus, another well sought after vaccine candidate, initially had a vaccine in the 1980s which produced more severe infections when a vaccinated individual was infected with another serotype due to the enhancement of viral uptake by the vaccine-induced antibodies. Whether a heightened immune response or promotion of viral infection, there remains the possibility of the same adverse events occurring with COVID19 vaccines. SARS-Cov2 is becoming well known for its related multisystem inflammatory syndrome in children as an illness stemmed in a type of immune response. Although not yet seen among clinical vaccine trials involving adult aged patients, there is still a risk when these vaccines against COVID19 are brought over to children. At the other end of the spectrum of a potential vaccine, responses are limited, unreliable response. When scientists attempted to produce a live, attenuated RSV vaccine, some recipients obtained prolonged viral shedding with little to no protection against the wild type virus. Shedding of SARS-Cov2 for prolonged periods of time could potentially produce local outbreaks and the exposure of some of the most vulnerable patients. Although the path to a safe and effective vaccine appears clearer for adults, it remains not the case for children, pregnant women, and immunocompromised people.
| Conclusion|| |
With such a variety of vaccine products being studied and all utilizing a gamut of scientific mechanisms, there is hope that at least one, if not many, will help attenuate the ongoing pandemic. Physicians should continue to look to the leading regulatory agencies for guidance around vaccine safety and efficacy with appropriate comparison trials upcoming.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al
. An mRNA vaccine against SARS-CoV-2 – Preliminary Report. N Engl J Med 2020;383:1920-31.
Poland GA, Ovsyannikova IG, Kennedy RB. SARS-CoV-2 immunity: Review and applications to phase 3 vaccine candidates. Lancet 2020;396:1595-606.
Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al
. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: A randomised, double-blind, placebo-controlled, phase ½ trial. Lancet Infect Dis 2021;21:39-51.
Gao Q, Bao L, Mao H, Wang L, Xu K, Yang M, et al
. Development of an inactivated vaccine candidate for SARS-CoV-2. Science 2020;369:77-81.
Burki TK. The Russian vaccine for COVID-19. Lancet Respir Med 2020;8:e85-6.
Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatulin AI, Shcheblyakov DV, Dzharullaeva AS, et al
. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: Two open, non-randomised phase ½ studies from Russia. Lancet 2020;396:887-97.
Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al
. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99-111.
Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, et al
. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): A single-blind, randomised, controlled, phase 2/3 trial. Lancet 2021;396:1979-93.
Bunyavanich S, Do A, Vicencio A. Nasal gene expression of angiotensin-converting Enzyme 2 in children and adults. JAMA 2020;323:2427-9.
Behl T, Kaur I, Bungau S, Kumar A, Uddin MS, Kumar C, et al
. The dual impact of ACE2 in COVID-19 and ironical actions in geriatrics and pediatrics with possible therapeutic solutions. Life Sci 2020;257:118075.
Leeb RT, Price S, Sliwa S, Kimball A, Szucs L, Caruso E, et al
. COVID-19 trends among school-aged children – United States, March 1-September 19, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1410-5.
Acosta PL, Caballero MT, Polack FP. Brief history and characterization of enhanced respiratory syncytial virus disease. Clin Vaccine Immunol 2016;23:189-95.
Tirado SM, Yoon KJ. Antibody-Dependent Enhancement of Virus Infection and Disease. Viral Immunol 2003;16:69-86.
Fulginiti VA, Eller JJ, Sieber OF, JoynerJW, Minamitani M, Meiklejohn G. Respiratory virus immunization: A field trial of two inactivated respiratory virus vaccines; an aqueous trivalent paratnfluenza virus vaccine and an alum-precipitated respiratory syncytial virus vaccine. Am J Epidemiol 1969;89:435-48.
Kapikian AZ, Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE. An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol 1969;89:405-21.
Bolles M, Deming D, Long K, Agnihothram S, Whitmore A, Ferris M, et al
. A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge. J Virol 2011;85:12201-15.
Halstead SB. Immune enhancement of viral infection. Prog Allergy 1982;31:301-64.
Karron RA, Buonagurio DA, Georgiu AF, Whitehead SS, Adamus JE, Clements-Mann ML, et al
. Respiratory syncytial virus (RSV) SH and G proteins are not essential for viral replication in vitro
: Clinical evaluation and molecular characterization of a cold-passaged, attenuated RSV subgroup B mutant. Proc Natl Acad Sci U S A 1997;94:13961-6.