The Janssen vaccine for COVID-19: Phase I/II
The vaccines previously reported on in this issue of TreatmentUpdate use messenger RNA. However, for its COVID-19 vaccine, the Janssen corporation is using a modified form of a virus called an adenovirus.
About adenoviruses
Adenoviruses are a group of viruses that can cause a range of illness from colds to pink eye to diarrhea to pneumonia.
Adenoviruses as vaccines
For decades scientists have been experimenting with adenoviruses, removing parts of their genetic material that cause disease and replacing them with instructions to make proteins for other viruses. In this way, the outer layer or form of the adenovirus is used as a carrier for transmitting information to cells. Viruses that are used in this way are called vectors. The adenovirus shell protects the genetic instructions that are the key part of the vaccine.
Modified adenoviruses (with the disease-causing parts removed) are used as vectors because they are very good at both protecting the genetic information they carry and getting this information inside a cell.
Once the modified adenovirus gets its cargo of genetic material inside the cell, the cell begins to produce proteins from another virus chosen by scientists. These proteins are released into circulation, where cells of the immune system encounter them. The cells of the immune system capture the viral proteins and take them to lymph nodes and lymphoid tissues. There, the viral proteins are displayed to many cells of the immune system. One group of immune system cells—B-cells—begins to produce antibodies against the viral proteins. Another groups of cells—T-cells, particularly CD8+ cells—learns to recognize the protein and produces antiviral substances in response. The immune system then creates many copies of these B- and T-cells, and some of them leave lymph nodes and related tissues and enter circulation. When they encounter SARS-CoV-2 in the future, these B- and T-cells can respond with antibodies and antiviral substances and greatly reduce the risk of developing COVID-19.
Adenoviruses have been modified to make vaccines for Ebola virus and also experimental vaccines for HIV and Zika virus.
Adenovirus 26 for COVID-19
The Janssen corporation is using a modified adenovirus called adenovirus 26 into which it has inserted the genetic information to instruct cells to make a protein used by SARS-CoV-2. Antibodies to this protein prevent SARS-CoV-2 from attaching to cells and infecting them.
Phase I/II
The Janssen corporation has released data from a complex phase I/II study of the vaccine that had enrolled about 800 people. In this study, participants received one or two injections of a low-dose or high-dose vaccine or placebo.
Common side effects included the following:
- fever
- fatigue
- headache
- muscle pain
- pain at the injection site
In general, these side effects were mild to moderate, appeared within two days of vaccination and resolved shortly thereafter.
About a month after receiving the first dose of the vaccine, at least 90% of participants had antibodies that attacked SARS-CoV-2. By 57 days after the first dose, this figure had reached 100%. This occurred regardless of the amount of vaccine administered. People who received a second shot of the vaccine had greatly increased antibody levels compared to the time after they had received only one injection.
Scientists found that two weeks after the initial vaccination blood samples from vaccinated people contained T-cells that could recognize SARS-CoV-2.
—Sean R. Hosein
REFERENCES:
- Mercado NB, Zahn R, Wegmann F, et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature. 2020 Oct;586(7830):583-588.
- Sadoff J, Le Gars M, Shukarev G, et al. Interim results of a phase 1-2a trial of Ad26 COV2 S Covid-19 Vaccine. New England Journal of Medicine. 2021; in press.
- Custers J, Kim D, Leyssen M, et al. Vaccines based on replication incompetent Ad26 viral vectors: Standardized template with key considerations for a risk/benefit assessment. Vaccine. 2021; in press.
- Kremer EJ. Pros and cons of adenovirus-based SARS-CoV-2 vaccines. Molecular Therapy. 2020 Nov 4;28(11):2303-2304.
- Bos R, Rutten L, van der Lubbe JEM, et al. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 spike immunogen induces potent humoral and cellular immune responses. NPJ Vaccines. 2020 Sep 28;5:91.