New crown vaccine "one shot a year" is still controversial, China to follow?

Read Time:13 Minute, 49 Second

Recently, the U.S. Food and Drug Administration (FDA) released its “Updated Proposal to Simplify New Crown Vaccination,” saying that in the future, the New Crown vaccine may be updated and promoted once a year, as is the case with the flu vaccine.

The FDA and other agencies are said to be considering holding a meeting in June each year to discuss and select the most likely prevalent strain or strains of the new crown virus and prepare an updated version of the vaccine by September of that year. Healthy individuals with a history of vaccination or at least two new crown infections should complete 1 dose of the vaccine in the fall to restore immune protection. High-risk groups such as young children, the elderly, and those with low immunity need 2 doses of vaccination per year.

Virologist and professor of biomedical sciences at The University of Hong Kong Li Ka Shing Faculty of Medicine, Kim Dong-Yan, told Medical Daily that considering the endemic phase of NCC around the world, there were earlier calls for the WHO to take the lead in promoting a unified annual vaccination program. Now, the United States has taken the lead.

According to comprehensive media reports, the FDA will meet in May and June this year to vote on the aforementioned proposal in order to decide on the specific implementation method. The academic community generally agrees that “vaccination should be simplified,” but there is controversy over the operational details. The rapid iteration of new coronaviruses and the absence of seasonal epidemic patterns, as well as the lack of effectiveness of once-a-year vaccination against infection and the difficulty of maintaining it into the next year, are among the more controversial issues.

Two days before the FDA-related meeting, Joachim Hombach, executive secretary of WHO’s Advisory Expert Group on Immunization Strategies, said that annual vaccination against neocrown is appropriate, but the key is to find the best timing – “one that balances The ideal timing of immunity decline, vaccination benefits and vaccination costs.”

“Annual change” is the reality

“It’s time to discuss and update the vaccination strategy for the new crown vaccine.” Dr. Nianshang Wang, a senior scientist at a leading U.S. pharmaceutical company, told Medical Daily that the BA.4/5 bivalent New Crown vaccine was approved in the U.S. in September 2022, with clinical data referencing the bivalent vaccine against the BA.1 strain and other data, and a streamlined approval process. At the time, it was predicted that the New Crown vaccine preparation, approval, and vaccination would follow a model similar to that of the flu vaccine. Anthony Fauci, who was then the White House chief medical advisor, also publicly stated that an annual New Crown vaccination, like the flu vaccine, might be required in the future.

On the one hand, this is either the inevitable result of a standing vaccination. Virologist Chang Rongshan has summarized the mutation pattern of the new coronavirus, which generally tends to increase transmission and immune escape and continue to decrease pathogenicity. However, he told the medical community that since the emergence of Omicron BA.4/5, it is reasonable to assume that the transmission and immune escape of its subsequent mutant strains are nearing a ceiling, and that the decrease in pathogenicity is not significant. This may lead to a high rate of repeat infections with new crowns, in individuals with low preexisting antibodies in the body or recurrent symptoms, where the symptoms of infection do not necessarily abate.

Aubrey Gordon, an epidemiologist at the University of Michigan who conducted a cohort study of Nicaragua, the largest country in Central America, also found that a history of prior infection did not prevent another symptomatic infection. “It’s more dangerous than the flu. I used to think that the new crown could end up being the coronavirus that causes the common cold.” Aubrey-Gordon told the media. A related study was published in December 2022 in the New England Journal of Medicine.

Real-world data, including the Cleveland Clinic Employee Study, suggest that infection superimposed on vaccination decreases both the rate of repeat New Crown infections and symptom severity. Conversely, natural infections or vaccinations alone make it difficult to establish effective immune protection.

“Without booster vaccination, about three months after natural infection, the rate of neutralizing antibody positivity in the population drops to a very low level and the immune escape enhancing mutant strain breaks free, creating a new wave of infection. After the full liberalization on January 8, China will definitely be affected.” Chang Rongshan told Medical Daily that Singapore is the other side of the coin.

Since this year, the average daily number of new infections in Singapore is less than 1,000, and the new R0 value (the basic number of infections) has dropped to 0.67. The mortality rate of those who have not completed vaccination is only 0.062%. Chang Rong San speculates that Singapore is less likely to be affected by New Crown again in the coming months, which is related to its high vaccination rate and high natural infection rate. Singapore has experienced multiple waves of infections such as Delta, Omicron and XBB. As of January 24 this year, 83% of the Singaporean population had “minimum immune protection”, i.e. 3 doses of mRNA or Novavax vaccine, or 4 doses of inactivated vaccine. On top of this, 50% of the population had completed the “renewal vaccination”, i.e. one more dose within 5 months to 1 year after obtaining the minimum protection.

On the other hand, “a one-year vaccination against Neocon is a compromise,” Wang said, explaining that there are few “immune depressions” in the world and the acute phase of Neocon transmission is over. Considering the iterative speed, immune escape and transmission of the new crown virus, as well as the technology of vaccine preparation and the characteristics of the platform, “annual vaccination” is a more universal strategy.

“Since the outbreak, scientists around the world have invested in surveillance and research using modern virology and molecular biology tools, including rapid whole-genome sequencing of the virus. This has helped us to get a clearer picture of the prevalence of different virus strains in the past and present. At the same time, the background of population immunization in the past 3 years on a global scale, including historical infection data, vaccine types and vaccination numbers in different places, is also very clear.

Combining these two pieces of information allows the scientific community to build models in the laboratory to predict the transmission potential of novel strains in specific population immunization contexts, and thus update vaccines accordingly.” Wang notes that the “annual update strategy” is applicable to all types of new crown vaccine technology platforms, including some recombinant protein vaccine preparation platforms in China, and is not difficult to implement.

“If the vaccine has to be updated several times a year, the requirements are much higher. This involves whether the platform can replace strains quickly and efficiently, and whether it can scale up capacity quickly. Semi-annual updates are more difficult for any vaccine platform to do. And of course the bigger challenge is the willingness of the population to get vaccinated.” Wang Nianshang said.

Financial investment may also constrain vaccine turnover. “Especially now that the U.S. Congress is no longer injecting money into the new crown vaccine, money has to be spent especially wisely to achieve optimal cost effectiveness.” Celine Gounder, an epidemiologist and senior fellow at the Kaiser Family Foundation, said.

“Once-a-year” vaccination may be too late

Peter Marks, head of the FDA’s Center for Biological Evaluation and Research, told the conference that winter is a high season for many respiratory infections. In the fall and winter of 2022, for example, there will be a “triple epidemic” of neocon, influenza and respiratory syncytial virus in the United States, with medical resources approaching alert levels in many places. A future vaccination in the fall may help to avoid a surge in emergency room visits and hospitalizations in the winter, and help to relieve medical pressure.

“The idea of one shot a year just sounds good.” Angela Shen, a vaccine specialist at Children’s Hospital of Philadelphia in Pennsylvania, believes the new coronavirus does not show a seasonal epidemic pattern and iterates much faster than the flu virus. The practice of updating the composition of the flu vaccine once a year is “probably too late” for the new crown vaccine.

Chang Rongshan explained that the influenza vaccine update schedule is based on well-documented seasonal epidemic patterns. Vaccine strains for the Northern Hemisphere are predicted based on previous Southern Hemisphere epidemics. Influenza vaccine preparation has experienced strain prediction errors in the past 10 years, such as the influenza wave in Hong Kong, China, in 2016, but overall predictions were more reliable. If epidemic patterns are not found, it is difficult to confirm the timing and frequency of vaccination and to improve vaccination efficiency.

“There is no seasonal epidemic pattern for the new crown, at least not this year,” he said, describing that in 2022, Singapore and Japan, which have high vaccination rates, both experienced 3 waves of infection, distributed in spring, summer and autumn, each time dominated by a different variant strain. More than 3 years into the new crown pandemic, the United States has seen a surge in infections almost every summer and winter. Moving forward in time, the Delta variant strain first appeared in India in October 2020 and has since caused a pandemic. The climate there is tropical, with hot temperatures all year round. The following June and July, there was an outbreak of Delta in Guangzhou, China. “To put it in perspective, the spread of the new crown is year-round.”

“Influenza does not cause such a long spread and such a large number of infections. Most people have either been exposed to influenza viruses or vaccinated before their immune systems matured. But the new coronavirus is too new. Most people worldwide are adults when they first become infected, a time when the immune system is less resilient, making it difficult to reduce the severity of infection, even if immune protection is generated. Or it would take a generation or two for the neo-crown infection to reach a steady state.” Aubrey Gordon told the media.

John Gerrard, chief health officer of Queensland, Australia, is a little more optimistic. He believes it may take “a few years” for the new coronavirus to evolve into a seasonal epidemic pattern. “Until then, we need to protect ourselves, flatten the infection curve of multiple times a year, reduce the symptoms of infection and extend the time between infections.”

The changing transmission characteristics of the virus as it mutates into the Omicron era also challenge the “vaccine year change strategy. “From Alpha to Delta, the early years of the epidemic were characterized by the sequential emergence of different mutant strains that replaced the previous one and caused a pandemic. In the year or so since the emergence of Omicron, there have been multiple simultaneous global epidemics, rather than one strain dominating the world. The epidemic strains may vary from place to place depending on the immune context. Currently, WHO is monitoring more than 300 simultaneous Omicron sublines. It is not clear whether future epidemics will be dominated by one mutant strain or a cluster of multiple strains.” Tom Peacock, an epidemiologist at Britain’s Imperial College, said.

Jenny Harries, head of the UK Health and Safety Executive (UKHSA), was quoted in the Financial Times as also referring to the “high degree of unpredictability.” “In some ways, new coronaviruses are less predictable than they were at the start of the outbreak and require continuous monitoring of a large number of new mutant strains.” This may mean that it is difficult to coordinate neo-crown vaccine components on a global scale.

Wang Nianshang noted that many laboratories, including the team of Yunlong Cao at Peking University, have been able to predict the epidemiological trends of virus strains in the coming months with relative accuracy based on existing mutant strains. It is still difficult to predict distant trends, such as mutations and epidemic trends in 2024.

There is also concern that having been infected with the original strains of the new crown or having received the corresponding vaccine may weaken the effectiveness of the updated version of the vaccine against the new strains. This phenomenon is known as “antigenic guilt” or “immune imprinting. (Click on “New Study: Three Doses of Vaccine Have Lower Antibodies Than Two Doses, How Do You Vaccinate? Learn more)

According to Jin Dongyan, the new crown vaccine can be made polyvalent, containing multiple strains of influenza vaccine. mRNA new crown vaccine is more protective and can maintain its protective efficacy for nearly one year even if there is an iteration of the strain. Countries and regions that primarily vaccinate with this type of vaccine can learn from the one-year update strategy.

Jerry Weir, director of the Division of Viral Products in the FDA’s Office of Vaccine Research and Review, said that if a new high-risk variant emerges after the “annual update strategy” is implemented, the FDA may hold an emergency meeting to discuss iterations of the vaccine and whether to give an additional dose. The members of the FDA tend to hold such meetings several times a year to avoid the misconception that the “annual update strategy” gives the public the impression that new strains are only a threat in the fall and winter, and that people can only be protected during this limited window of time.

How China’s vaccination strategy is following suit

Many places around the world are considering adjusting their vaccination strategies for Neospora. The Hong Kong region is also exploring that the actual frequency of vaccination in the future may have to be more intensive and more frequent than one flu shot per year.

Chang said that based on the type of vaccination and previous infections in China, there may be at least two waves of new crown infections in China in 2023, and only further boosting of vaccination can reduce the number of hospitalizations and deaths, calling for people over 45 years old to receive booster shots.

He added that for those infected in December 2022, a booster vaccination is recommended by April this year. The preferred choice is a polyvalent vaccine containing the omicron subline. You can also choose the recombinant protein vaccine + nasal inhalation vaccine combination, with one dose of each, which will achieve the best protection rate among the available domestic vaccine options.

“China’s main vaccination is different from Europe and the United States, and the ‘annual shift strategy’ is not suitable for China unless the mRNA vaccine is approved urgently.” Jin Dongyan said that vaccines against new subtypes of omnicron need to be developed and marketed quickly.

The U.S. released infection data from Dec. 1, 2022, to Jan. 13, 2023, supporting the effectiveness of Omicron BA.4/5 bivalent vaccination, saying it would reduce the risk of symptomatic infection by nearly 50 percent. Compared to those who did not receive the bivalent vaccine, the risk of new coronary death was reduced by nearly 13 times in those who received it.

Several interviewees pointed out that China should strengthen surveillance of new coronaviruses and explore epidemic patterns. China has built a surveillance direct reporting network for influenza viruses, and after collecting respiratory samples, one sample can be used for both influenza and new crown, and a sample will be taken for viral whole-genome sequencing to monitor changes in the epidemiological spectrum of new crown and influenza viruses.

“Our new crown epidemic strain turnover is two to three months later than the global, but will be synchronized with the world in 2023. Our country is so vast that if a new pandemic strain emerges in a region, it will be difficult for the existing surveillance system to detect it in time. Under the ‘Category B’ control policy, it is particularly important to monitor epidemic strains, especially those imported from abroad. Early detection of trends in strain turnover will enable early action.” Chang Rongshan said.

Source.

1.Should COVID vaccines be given yearly? Proposal divides US scientists.