NEJM: Decreased protection efficiency of mRNA and adenovirus vaccines against delta mutant

On August 12, 2021, data on the efficiency of real-world vaccine protection in the United Kingdom was published in the New England Journal of Medicine (NEJM).

Since the global outbreak of the COVID-19 epidemic in early 2020, various mutant strains have continued to emerge, including Alpha mutant strain, which first appeared in the UK, and the Delta mutant strain first appeared in India. Among them, the Delta mutant strain has become the main SARS-CoV-2 strain worldwide, and some studies suggest that these mutants may have greater transmissibility and immune escape, making it critical to determine the effectiveness of current vaccines (https://www.creative-biolabs.com/vaccine/) against these mutants.

The Delta mutant strain is characterized by the presence of mutations in its spike protein (S protein), such as T19R, Î157-158, L452R, T478K, D614G, P681R, and D950N. Among them, the L452R and T478K mutations lead to enhanced immune escape ability, while the P681R mutation leads to enhanced replication ability, resulting in higher viral load and greater infectivity.

On August 12, 2021, the New England Journal of Medicine (NEJM), one of the top four international medical journals, published data on the efficiency of real-world vaccine protection in the United Kingdom.

This study showed that the mRNA vaccine (BNT162b2) and the adenovirus vector vaccine (ChAdOx1
CoV-19), although still protecting against the Delta mutant strain, had a substantially reduced protection efficiency.

The protection efficiency against the Delta mutant strain was 88.0% with two doses of BNT162b2 vaccine and 67.0% with two doses of ChAdOx1
CoV-19 vaccine.

In contrast, the protection efficiency of these two vaccines against the original strain of SARS-CoV-2 was 95% and 90%, respectively. The protection efficiency against the Alpha mutant strain was 93.7% and 74.5%, respectively.

In addition, the study noted that the protection efficiency was only 30.7% with only one dose of mRNA vaccine (BNT162b2) or adenovirus vector vaccine (ChAdOx1
CoV-19). In contrast, the protection efficiency against the Alpha mutant strain was 48.7% with only one dose of vaccination. This reminds us of the undesirability of vaccinating with only one dose or too long an interval between doses.

Finally, the team indicated that after two doses of vaccine, the protection efficiency of the vaccine against the Delta mutant strain decreased compared to that of the Alpha mutant strain, but the decrease was not significant, indicating that the mRNA vaccine and the adenovirus vaccine still had good protection efficiency against the Delta mutant strain. However, it should be noted that for both vaccines, the efficiency of protection against Delta mutant strains was poor at 30.7% with only one dose.

mRNA vaccinernmRNA is a genetic material that transmits DNA genetic information and guides protein coding.

Non-replicating mRNA Vaccine (https://www.creative-biolabs.com/vaccine/non-replicating-mrna-vaccine-platform.htm): Encoding the antigen of interest and contains 5’ and 3’ untranslated regions (UTRs).
Self-amplifying mRNA Vaccine: Encoding not only antigen of interest but also viral replication machinery that enables intracellular RNA amplification and abundant protein expression.

Technical highlights of mRNA vaccine
* Non-infectious and non-integrating.
* In vivo half-life can be regulated.
* The inherent immunogenicity of the mRNA can be down-modulated.

Adenovirus (Ad) vector vacciner
Adenoviruses are double-stranded DNA viruses with a genome of 34~43 kb, a size that is amenable for easy manipulation. Ad vectors present several advantages as vaccine vectors and achieve the most important criteria for an ideal vaccine vector in efficacy, safety, and stability.

Technical highlights of Ad as vaccine vector
* Ad vectors have strong immunity when administered through parenteral (subcutaneous, intravenous, intramuscular, or intraperitoneal) or mucosal (oral or intranasal) routes.
* Can infect a wide range of both actively dividing as well as post-mitotic quiescent mammalian cells.
* Safe without the potential risk of insertional mutagenesis as Ad vector genome does not integrate into the chromosome and mostly remains epichromosomal.