In the just-concluded NPC & CPPCC, it is stated by the report on the work of the government that as China has entered a phase of regular Covid-19 response, in which prevention and control measures for Class B infectious diseases are applied, COVID-19 vaccines should be upgraded. Based on previous experience of global COVID-19 pandemic, population immunity established after the peak of an epidemic will decrease in several months’ time. Vaccines are recognized as effective tools to combat with future uncertainties of the pandemic. What kind of vaccine is more effective? What does an upgraded version of COVID-19 vaccine should be like? 

Domestic leader in mRNA vaccine development, AIM Vaccine (06660.HK), is fully prepared to drive the upgradation of COVID-19 vaccines. According to the company's latest announcement, its bivalent Delta+Omicron BA.5 mRNA vaccine has been approved for Phase III clinical trial in Pakistan. Previously conducted clinical studies in China have proved good safety. Outcomes of virus neutralization assay showed that the vaccine candidate can induce high levels of neutralizing antibodies against Delta, Omicron BA.5, BQ.1 and XBB variants of SARS-nCoV-2.

We interviewed AIM Vaccine's Chief Research Officer, Zhang Fan, on the heated topics of COVID-19 vaccine upgradation to gain insights from industry experts.

1. Which vaccine is the most effective?

Zhang Fan: According to the latest real-world studies, bivalent mRNA vaccines currently provide comprehensive protection against infections, severe illnesses and deaths.

Real-world data released by US CDC on December 2, 2022 shows that the protection against symptomatic COVID-19 infection can be increased by up to 56% via vaccination of bivalent COVID-19 mRNA vaccine compared with that of previous vaccination.

On December 16, 2022, US CDC published a study on the efficacy of a bivalent COVID-19 in preventing hospitalization among people aged 65 and older. The results showed that compared to unvaccinated individuals, the protection of elderly people who received a booster of bivalent mRNA vaccine was 84% in preventing COVID-19 hospitalizations. Compared to those who received more than 2 shots of vaccine against original SARS-nCoV-2 strain at least two months before, elders who received booster of bivalent mRNA vaccine had a 73% increase in efficacy of preventing COVID-19 hospitalizations. Moreover, the longer the interval between previous vaccination with original strain vaccines and symptom onset, the higher was the relative efficacy for bivalent mRNA booster, which could be up to 83%. 

Bivalent Delta + Omicron BA.5 COVID-19 mRNA vaccine has achieved promising outcomes in two clinical trials in China, which proves good protection of the bivalent mRNA vaccine. The subjects of these two clinical trials were adults over 18 years old who had not received any COVID-19 vaccine or been infected with SARS-nCoV-2. Clinical studies have shown that this vaccine candidate has good safety. In addition, the results of virus neutralizing assays show that the vaccine can induce high levels of neutralizing antibodies against Delta, Omicron BA.5, BQ.1 and XBB variants of SARS-nCoV-2.

2. Why are multi-valent vaccines superior?

Zhang Fan: Currently, SARS-nCoV-2 is mutating rapidly and new mutants could replace previous mutants in a few months’ time. It is not easy to develop a vaccine to fully match each mutant, but multi-valent vaccines with broad-spectrum coverage are believed to be an ideal solution for mutation. In theory, multi-valent vaccines stimulates the human body to produce a broader range of antibodies, even if new mutants do not match all components in the multi-valent vaccine, there will still be relatively good protection.

According to the data from real world studies, marketed bivalent vaccine shows better broad-spectrum performance against Omicron mutant which has stronger immune escape ability. On November 18th, 2022, German company BioNTech released the neutralization data of Omicron BA.4/5 bivalent vaccine against the latest epidemic strains. The study showed that after receiving a fourth dose of Omicron BA.4/5 bivalent vaccine, neutralizing antibody titers against BA.5 sublineage variants (BA.4.6, BQ.1.1 and XBB.1) and BA.2 sublineage strains (BA.2.75.2) increased by 8.7 times (95%CI: 5.7, 13.3) and 4.8 times (95%CI: 3.3, 6.9), respectively. Compared with a monovalent vaccine booster for the original strain, neutralizing antibody titers increased by 3.2 to 4.8 times.

3. Can mRNA vaccines be a solution to the virus mutations?

Zhang Fan: Apart from the aforementioned data from experiments and real-world studies, mRNA technology has its strength in solving the problem of virus mutations by its speed.

The main characteristic of this technology platform is that mRNA can express any type of protein, and a production line can produce billions of vaccine products at a lower cost compared to traditional protein vaccines. The production cycle for mRNA vaccines is extremely short. By finishing GMP production and quality control within 1-2 months, it can be applied for massive outbreaks of diseases. mRNA vaccine is a platform technology with strong reusability.

In summary, this technology platform has the advantages of short development cycle, applicability of mass production and good efficacy, which will meet the practical needs of epidemic prevention and control.