COVID-19 Vaccines

Types of vaccines

Vaccines can stimulate the body to produce a protective immune response. The vaccine itself can mimic natural infection, but it does not actually cause illness. If a pathogen infected the body after vaccination, the immune system would quickly prevent the pathogen from spreading in the body and causing disease. Vaccines can be divided into the 3 types: inactivated pathogen, recombinant protein-based, and genetic vaccine. In general, inactivated pathogen and recombinant protein-based vaccines induce humoral immunity (Th2-biased) via MHC II pathway. Genetic vaccine such as mRNA and DNA vaccine can induce both cellular and humoral immunity via MHC I and MHC II pathways.


The emergence and rapid spread of a novel severe acute respiratory syndrome (SARS) like coronavirus SARS-CoV-2 is causing the global coronavirus disease 2019 (COVID-19) pandemic and destroying global health and economy. To date, SARS-CoV-2 has infected over 264 million people and caused more than 5.22 million deaths. Understanding how SARS-CoV-2 enters human cells is a high priority for deciphering its mystery and curbing its spread. Studies revealed that a virus surface spike protein mediates SARS-CoV-2 entry into cells by binding to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD). Therefore the spike protein is an excellent target for developing successful vaccine to protect from infection and curb the pandemic.


To date, there are two mRNA vaccines (Pfizer-BioNTech and Moderna) and two virus vector-based vaccines (JNJ and AstraZeneca) have been approved in USA and Europe, two or three inactivated vaccines has also been approved in China and India. There are a few other vaccines still in clinical trial stages. We briefly discuss as follows:


Genetic vaccines

Vaccines from Pfizer-BioNTech, Moderna, and Johnson & Johnson are being administered in the U.S. The FDA has authorized—and the CDC has approved—booster shots for all three vaccines, along with a “mix-and-match” approach that would allow people to choose a different vaccine for their booster than the one they started with. They are all genetic vaccines.


1. mRNA vaccines

Both Pfizer-BioNTech and Moderna vaccines are mRNA. Unlike vaccines that put a weakened or inactivated disease germ into the body, the mRNA vaccine delivers a tiny piece of genetic code from the SARS CoV-2 virus to host cells in the body, essentially giving those cells instructions, or blueprints, for making copies of spike proteins (the spikes you see sticking out of the coronavirus in pictures online and on TV). The spikes do the work of penetrating and infecting host cells. These proteins stimulate an immune response, producing antibodies (humoral immune response) and developing T cell and memory cell immune response that will recognize and respond if the body is infected with the actual virus.


Both vaccines showed about 95% efficacy in Phase 3 clinical trials with two shots (21-28 days interval). This figure has changed over time. At six months after vaccination both Pfizer and Moderna still are considered highly effective, several recent studies showed Moderna to be more protective. One study published in The New England Journal of Medicine found Moderna vaccine to be 96.3% effective in preventing symptomatic illness in health care workers compared to 88.8% for Pfizer. Another, from the CDC, found Moderna’s effectiveness against hospitalization held steady over a four-month period, while Pfizer’s fell from 91% to 77%. This research is still limited and more data is needed to fully understand the differences between the two vaccines.


Moderna reported that studies showed its vaccine is effective against the Beta, Delta, Eta, and Kappa variants, although it did show it to be about two times weaker against Delta than against the original virus. The Pfizer vaccine was found to be more than 95% effective against severe disease or death from the Alpha variant (first detected in the United Kingdom) and the Beta variant (first identified in South Africa) in two studies based on real-world vaccinations.


2. DNA vaccine

INOVIO's DNA vaccine candidate (INO-4800) against SARS-CoV-2, is composed of a precisely designed DNA plasmid that is injected intradermally followed by electroporation using a proprietary smart device, which delivers the DNA plasmid directly into cells in the body and is intended to produce a well-tolerated immune response. As one of the only nucleic-acid based vaccines that is stable at room temperature for more than a year, at 37°C for more than a month, has a five-year projected shelf life at normal refrigeration temperature and does not need to be frozen during transport or storage, INO-4800 is anticipated to be well-positioned for a primary series immunization as well as a booster. Currently this DNA vaccine is under Phase 3 clinical trials in multiple countries in Latin America, Asia, and Africa. Regulatory authorization in India follows authorizations from health authorities in Brazil, Philippines, Mexico and Colombia.


3. Virus vector-based vaccine

Johnson & Johnson and Oxford-AstraZeneca have developed similar virus vector-based COVID-19 vaccines. Unlike the mRNA vaccines, virus vector-based vaccines can be stored in normal refrigerator temperatures, and because it requires only a single shot, it is easier to distribute and administer.


The virus vector-based vaccines use a different approach than the mRNA vaccines to instruct human cells to make the SARS CoV-2 spike protein. Scientists engineer a harmless adenovirus as a shell to carry genetic code on the spike proteins to the cells. The shell and the code cannot make you sick, but once the code is inside the cells, the cells produce a spike protein to train the body’s immune system, which creates antibodies and memory cells to protect against an actual SARS-CoV-2 infection.


Both vaccines obtained similar overall efficacy (75%) and over 85% efficacy against moderate and severe disease.


Johnson & Johnson reported in July 2021 that its vaccine is also effective against the Delta variant, showing only a small drop in potency compared with its efficacy against the original strain of the virus, although one recent study suggested that the J&J vaccine is less effective against Delta.



Recombinant S protein-based or peptide vaccine

1. NovaVax

NovaVax has developed a recombinant Spike protein vaccine which is highly effective in clinical trials. It is simpler to make than some of the other vaccines and can be stored in a refrigerator, making it easier to distribute. Unlike the mRNA and vector vaccines, the Novavax vaccine takes a different approach. It contains the spike protein of the coronavirus itself, but formulated as a nanoparticle, which cannot cause disease. When the vaccine is injected, this stimulates the immune system to produce antibodies and T-cell immune responses.


Studies have shown 90% effectiveness against lab-confirmed, symptomatic infection and 100% against moderate and severe disease in Phase 3 trial results released in a company statement in June. The company says the vaccine was 91% protective of people in high-risk populations such as people older than 65, those with health conditions that increase risk of complication, and those in situations where they are frequently exposed to the virus.


2. Virus-like particles

The company VBI has developed virus-like particle vaccine ( VBI-2900) that consists of three enveloped virus-like particle (eVLP) vaccine candidates: (1) VBI-2901, a trivalent pan-coronavirus vaccine expressing the SARS-CoV-2, SARS-CoV, and MERS-CoV spike proteins, (2) VBI-2902, a monovalent COVID-19-specific vaccine expressing the native SARS-CoV-2 spike protein, and (3) VBI-2905, a monovalent COVID-19-specific vaccine expressing the spike protein from the Beta variant (also known as B.1.351). The vaccine program has been developed through collaborations with the National Research Council of Canada (NRC), the Coalition for Epidemic Preparedness Innovations (CEPI), and the Government of Canada, through their Strategic Innovation Fund.


In Phase 1 study, VBI-2902a induced neutralization titers in 100% of participants, with a GMT of 329, 4.3x the GMT of the convalescent serum panel, after two doses. After two doses, VBI-2902a also induced antibody binding titers in 100% of participants, with a GMT of 4,047 units/mL, 5.0x the GMT of the convalescent serum panel


3. Peptide vaccine

Emergex announced approval to initiate Phase I clinical trial of its next generation COVID-19 vaccine candidate in November. This is a synthetic peptide vaccine designed to prime T-Cells to rapidly remove viral-infected cells from the body after infection. This vaccine may offer broad immunity against SARS-CoV-1 and all SARS-CoV-2 variants and provide long-lasting immunity that does not require seasonal booster vaccines.


Emergex vaccines have been designed to be administered via the skin using micro needles and to be stable at ambient room temperature for more than three months, facilitating rapid and efficient distribution across the world and making administration of the vaccine more patient friendly.


Inactivated virus vaccine

Inactivated COVID-19 vaccines have also been approved in China (developed by Sino Biologics and Beijing Kexing) and in India (developed by Bharat Biotech).

(Scudellari M. Nature, 2021, 595:640-644)



Written by: Feng Lin, M.D., Ph.D.



References:

1. Scudellari M. Nature, 2021, 595-640-644

2. Shang J, Wan Y, Luo C, et al. PNAS, 2020, 117:112-11734