Caixin
Nov 15, 2021 06:47 AM
CHINA

Cover Story: Finding the Best Toolkit for Containing Covid-19

Since late October, residents of northeast Beijing’s Chaoyang district have received notices recommending a third shot of Covid-19 vaccines. People lined up for booster shots at long-closed neighborhood inoculation sites that reopened.

Beijing joined several Chinese cities and provinces offering boosters to the public as new outbreaks of the highly transmissible delta mutation spread, testing the country’s year-long immunization efforts.

As of Nov. 10, China administered two shots of Covid vaccines to more than 1 billion people, over 75% of the population. In October China started nationwide inoculations for children ages 3–11.

The push for booster shots and vaccination of kids reflects China’s pressing need to build more-secure lines of defense against the persistent pandemic as new variants prevail and the protection of existing vaccines declines over time. Drugmakers are developing new, more-effective shots, but investor funding is drying up as conducting new clinical trials grows more expensive.

In a new wave of virus resurgence since the national holiday in October, flare-ups spread across more than 10 provinces, sparking concerns over the efficacy against the variants of China’s widely used vaccines based on inactivated virus.

Sticking to its Covid-zero strategy, China also faces mounting pressures as more countries shift to coexisting with the virus by relaxing restrictive measures and reopening borders. China’s high population density and shortfall of health-care resources means it must maintain strict disease control measures until a “barrier of immunity” has been established, health experts said.

Recent progress in developing Covid-19 pills by global pharmaceutical giants Pfizer Inc. and Merck & Co. fueled hopes that humans will have more powerful weapons to alter the course of the pandemic. But there are uncertainties over the accessibility and affordability of the potential new drugs, experts said.

Vaccinations are still the top priority, and Covid pills could be a supplement, said Lu Mengji, a virologist at the University of Duisburg-Essen in Germany. The medicines will mainly be used to protect patients from becoming critically ill but can’t control the pandemic as vaccines do, Lu said.

Expanding vaccination coverage and enhancing the shots’ efficacy is still the best way to tame the virus, experts said. Countries like Israel, Singapore and the U.K. have been giving booster shots to certain groups of people

By administering booster shots to almost 50% of its population, Israel recently achieved a significant reduction in the prevalence rate of the virus, said Zhang Wenhong, the director of China’s National Center of Infectious Diseases and director of the Infectious Diseases Department of Huashan Hospital affiliated to Fudan University. China could learn from Israel’s experience, Zhang said.

 

Strengthening the barrier of immunity

China has approved three domestically made inactivated-virus Covid vaccines for children younger than 12. As of Oct. 29, 3.53 million doses of the vaccines were given to children between 3 and 11 in the first month since the inoculations began nationwide.

Some parents expressed concerns about vaccinations for their kids, partly because of a lack of complete clinical data. The currently available vaccines for children — developed by state giant Sinopharm’s Beijing Institute of Biological Products Co. Ltd. and the Wuhan Institute of Biological Products Co. Ltd., as well as Sinovac Biotech Ltd. — were approved for emergency use in children while Phase 3 clinical trials are still underway abroad.

But currently available data indicate that children tend to have a stronger immune response to vaccination than adults. In January, Sinopharm Chairman Liu Jingzhen said the company’s vaccines were proved safe for children in the first two phases of clinical trials.

Other countries have been inoculating children in different age groups. The United States approved vaccinations for children as young as 5 while most countries in Europe and Asia are offering shots to those 12 or older.

China moved to inoculate younger children because Covid-19 has shown equal danger to children, said Wang Huaqing, an immunity expert at the Chinese Center for Disease Control and Prevention (China CDC). Even though the early impression was that children were less vulnerable to the virus, data from many countries now show that childhood infections have been increasing, catching up to the pace for adults, Wang said.

Although China is approaching the 80% vaccination rate that health experts say is enough to form herd immunity, coverage rates among different age groups are highly divergent. With low inoculation rates among the elderly and kids, the risk of new outbreaks remains high, said Zhang Boli, an academician at the Chinese Academy of Engineering.

Vaccines’ declining efficacy over time and the prevalence of new virus variants also pose challenges to disease control.

As most countries started mass vaccinations about a year ago, the antibody levels of those who received early inoculations have declined, said Jiang Shibo, a medical professor at Fudan University.

Studies have shown different levels of reduced protection among all Covid vaccines. A study published in August in the journal Nature found that the efficacy rate of the mRNA vaccine developed by Pfizer and BioNTech dropped to 78% within 90 days after the second shot from 92% after 14 days. The viral vector vaccine from AstraZeneca showed an efficacy reduction from 69% to 61%, the study found.

The inactivated-virus vaccines developed by Sinovac also showed a significant drop in geometric mean titer, which measures the average antibody level, six months after full inoculation, according to a study published in July by the Jiangsu provincial CDC, Fudan University and Sinovac.

Current vaccines are also less protective against the highly transmissible delta variant. An August study by the U.S. Centers for Disease Control and Prevention showed that the mRNA vaccines’ efficacy rate against the delta variant dropped to 66% from 91% against earlier variants.

A study led by China’s top infectious disease expert Zhong Nanshan based on a limited number of patients in southern China found that the protection rate of the two most-used inactivated-virus vaccines in China may drop to 59% against the delta variant, although they performed well to prevent critical illness.

Recent flare-ups in China showed the risks. According to official data, 15 of the 18 infected patients in Shandong’s Rizhao city received two inactivated-virus vaccine shots.

To bolster protection, China rolled out booster shots in at least 15 provinces starting in October. As of Nov. 6, 37.97 million people received the additional shot.

China currently limits the boosters to three inactivated-virus vaccines and the single-shot adenoviral vector vaccine developed by Tianjin-based CanSino Biologics Inc.

Expectations are rising that the innovative mRNA vaccines may become another option for boosters after a shot jointly developed by Chinese biotech company Walvax Biotechnology Co. and Suzhou Abogen Biosciences recently won administrative approval for a Phase 3b clinical trial.

The approval was granted to assess the efficacy and safety of using the mRNA vaccine as a booster shot for adults inoculated with inactivated-virus vaccines, according to public records on the Ministry of Science and Technology website. Meanwhile, Germany’s BioNTech and its Chinese partner Shanghai Fosun Pharmaceutical Co. Ltd. are also conducting final-stage tests of its widely used mRNA vaccine to launch in China. Ugur Sahin, BioNTech’s CEO, told Caixin earlier this month that the companies are working to deliver the mRNA vaccines in China, without giving a timetable.

MRNA vaccines have shown higher efficacy as booster shots than inactivated-virus shots, said Zeng Guang, former chief epidemiologist of the China CDC.

A China CDC official said the country will consider offering more options for booster shots and inoculation combination as collection of clinical data increases.

Authorities have also been closely monitoring changes in public immunity status including infection, severity and antibody levels to fine-tune the country’s vaccination strategies, the official said.

As of Nov. 10, China administered two shots of Covid vaccines to more than 1 billion people, over 75% of the population

Finding the best toolkit

Experts called for continued research to develop more effective vaccines to counter new variants as understanding of the virus deepens.

China has approved seven domestically developed Covid-19 vaccines for public inoculation, including five inactivated-virus shots, one recombinant adenovirus vector vaccine and one based on recombinant subunit protein technology.

Some companies are working to develop a second generation of Covid-19 vaccines. On Nov. 9, Jiangsu Recbio Technology Co. Ltd. published early-stage study results for a vaccine using protein engineering and new adjuvant technologies. Unlike most existing vaccines, the shot under development uses receptor-binding domain as an antigen, designed to trigger a stronger immune response.

But as the domestic outbreak wanes, studies of new vaccines face greater challenges to find enough patients for clinical trials. Most companies have to test vaccines overseas, driving up development costs.

At the same time, investor enthusiasm for backing vaccine development has cooled after last year’s market boom, meaning developers will find it more difficult to raise money to support their research.

Vaccines are still the most crucial weapon for taming the pandemic when countries move to adapt to co-existing with the virus, epidemiologists say.

“The precondition (for countries to relax virus control) is enough immunity of the public and a health-care system with sufficient capacity,” the University of Duisburg-Essen’s Lu said.

For China, further boosting public immunity and the efficacy of vaccines before it can relax controls is especially important as the country’s infection rate with the virus is very low. Thanks to drastic control measures in the early days of the pandemic, the natural infection rate of China’s 1.4 billion people is less than 0.001% compared with 20% to 50% in many other countries, said China CDC’s Zeng. But it also means the country needs greater vaccination coverage to form herd immunity, Zeng said.

China’s uneven distribution of medical resources and inadequate health-care capacity pose another major challenge. The most pressing issue for China is to strengthen vaccine protection rates to as high as 90%, “no matter by imports or domestic development,” Lu said.

As neighboring countries are reopening borders and easing disease-control measures, China needs a new strategy better suited to meeting the ongoing challenge while normalizing people’s lives and livelihoods, Zhang of the National Center of Infectious Diseases said.

“We need to establish the most sustainable and best combination of vaccines,” Zeng said. “China needs to explore how the vaccines can be combined to show the best efficacy.”

Contact reporter Han Wei (weihan@caixin.com) and editor Bob Simison (hello@caixin.com)

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