Key investment points
Covid-19 vaccine booster policy announcement, how to treat the effect and market space of different routes?
Event: on February 19, 2022, the joint prevention and control mechanism of the State Council held a press conference, The sequential enhanced immunization program of covid-19 vaccine in China is introduced: ① homologous enhancement: “target people over 18 years old who have been vaccinated with inactivated vaccines of Sinopharm Zhongsheng Beijing company, Wuhan company and Beijing Kexing company, as well as adenovirus vector vaccine of Tianjin Cansino Biologics Inc(688185) company for 6 months can receive one dose of secondary homologous enhanced immunization”, “Approved the homologous booster immunization of covid-19 virus inactivated vaccine of Shenzhen Kangtai company and the Institute of biology of Medical College”. ② Heterologous enhancement: “the recombinant protein vaccine of zhifeilongke horse or Cansino Biologics Inc(688185) adenovirus vector vaccine shall be used for sequential booster immunization”. Based on the clinical data of homologous / heterologous vaccination, this paper analyzes the safety / effectiveness and potential market space of different vaccination methods.
Heterologous sequence: better safety and effectiveness
We believe that from the clinical data, heterologous sequential immunogenicity is better than homologous enhancement. Adenovirus vector vaccine, recombinant protein vaccine and mRNA vaccine are safe, effective and well tolerated as booster needles, and the immunogenicity against delta or Omicron variants is relatively good. Comparison between different technical routes: the paper published in January 2022 compared Johnson & Johnson ad26 Cov2-s, Pfizer bnt162b2, chadox1ncov-19 of AZ and coronavac of Kexing. The results show that Pfizer mRNA vaccine has better immunogenicity. At the same time, the paper published in biorxiv studied the neutralizing antibody titers of two Chinese inactivated vaccines, Chongqing Zhifei Biological Products Co.Ltd(300122) zf2001 and Cansino Biologics Inc(688185) Providencia as booster needles under the first vaccination of coronavac and bbibpcorv of Beisheng Institute. The data showed that the neutralizing antibody titers of adenovirus vector booster needles were relatively higher. We believe that the sequential vaccination effect of different technical routes requires more head-to-head research and real-world data. From the perspective of each technical route:
① adenovirus vector vaccine: according to the research of Zhu Fengcai and Chen Wei of Jiangsu Provincial Center for Disease Control and Prevention (published in January 2022), from the level of euvirus neutralizing antibody, 2 doses of inactivated vaccine + 1 dose of Ad5 vector vaccine > 1 dose of inactivated vaccine + 1 dose of Ad5 vector vaccine > 3 doses of covid-19 inactivated vaccine > 2 doses of covid-19 inactivated vaccine. For delta mutant, sequential vaccination still induced higher antibody level. On the 14th day after sequential booster immunization, the GMT of neutralizing antibody was 6.7 times higher than that of homologous booster immunization, and the sequential basic immunization was 3 times higher than that of homologous basic immunization. For the Omicron variant, according to the biorxiv paper (published in January 2022), sinokvissa ® The level of neutralizing antibody against Omicron was 6 times higher than that of inactivated vaccine and 3 times higher than that of recombinant protein vaccine.
② recombinant protein vaccine: in terms of immunogenicity, the study of jingwenai et al. (published in January 2022) showed that compared with the third dose of inactivated covid-19 vaccine (coronavac), zf2001 induced humoral immune response was higher than that of coronavac. For the Omicron variant, the results of Xinzhao, Gaofu and others showed that (published in December 2021) 62.5% of the people who had been vaccinated with three doses of inactivated vaccine, 56.25% of the people who had been vaccinated with zf2001 (scheme 0,1,2) and 100% of the people who had been vaccinated with zf2001 (scheme 0,1,5) were positive for Omicron neutralizing antibody. In terms of neutralizing antibody titer, the neutralizing activity of Omicron in the serum group of rehabilitated patients decreased by 17.4 times compared with the original strain, 5.1 times in the inactivated vaccine group, 10.6 times in the zf2001 (0,1,2) group, but only about 3 times in the zf2001 (0,1,5) group, and the clinical data are better.
③ mRNA vaccine: a randomized controlled clinical trial (RCT) published by the research team in Hong Kong, China in November 2021 showed that adults who completed two doses of coronavac (Kexing Zhongwei inactivated vaccine) received a dose of bnt162b2 about 4 months after the second dose, which could induce a higher antibody immune level, The neutralization activity of different mutants (beta, gamma, delta) was higher than that of the homologous third dose coronavac enhancement group.
Homologous enhancement: the tolerance is good, and the immunogenicity is weaker than that of heterologous sequence
① immunogenicity: compared with 28 days after the second dose of Kexing Zhongwei inactivated covid-19 vaccine (coronavac), the neutralizing antibody level after the third dose increased by 3-5 times, but heterologous vaccination produced a stronger immune response than homologous vaccination. ② Response to mutant strains: after vaccination with inactivated vaccine and booster injection, a broad-spectrum neutralizing antibody is produced, which can effectively respond to the mutant strains. ③ Tolerance: relatively good, no difference compared with the previous two times. We believe that homologous enhancement is still an effective choice for enhanced needle inoculation, but the immunogenicity is relatively weaker than heterologous sequence.
Investment advice
Potential market space: a simple estimate is about 7-8 billion yuan. The core variables are purchase price, promotion mode and the proportion of heterologous vaccination. ① Vaccination status: according to the data of the National Health Commission, as of February 18, 2022, the total number of covid-19 vaccinations in China was 1.27 billion, and 1.23 billion people had been vaccinated in the whole process; According to ourworldindata, as of February 7, 2022, the total number of booster shots in China was 460 million, and the number of booster shots per 100 people was 31.8, higher than the global average (15.2). ② Potential space for booster needle vaccination: we assume that 60% of the vaccinated population is covered by booster needle and 1 booster needle per person, corresponding to the demand of 760 million needles; Subtract 460 million inoculated needles, corresponding to the incremental demand of 300 million needles. In terms of structure, we assume that heterologous vaccination accounts for 50% and homologous vaccination accounts for 50%, and simply assume that the government purchase price of inactivated vaccine is 20 yuan / dose and the purchase price of other vaccines is 30 yuan / dose, and the corresponding incremental booster needle demand is about 7-8 billion yuan. We believe that the estimated market space results are only for reference, and the variables that may affect the actual booster market space include ① vaccine purchase price, ② booster promotion and charging method, and ③ the proportion of heterologous vaccination.
From the perspective of impact on listed companies, we suggest paying attention to Cansino Biologics Inc(688185) , Chongqing Zhifei Biological Products Co.Ltd(300122) , Shenzhen Kangtai Biological Products Co.Ltd(300601) and other companies to strengthen vaccination promotion; We believe that the R & D and sales of covid-19 vaccine of Chinese vaccine companies are the embodiment of comprehensive ability. We also suggest to look at the ability transition of Chinese vaccine companies behind covid-19 vaccine opportunities from the perspectives of technical platform construction, international ability expansion and China’s commercialization ability improvement.
Risk tips
The risk that the clinical promotion speed of vaccine is lower than expected, the risk of changes in vaccine supervision / procurement policies, and the risk of production / transportation safety accidents.
