A new study suggests that a Sinopharm vaccine offers poor protection from COVID-19 among the elderly, raising questions for dozens of countries that have given the Chinese company’s shots to their most vulnerable populations.
A survey of blood samples taken from 450 people in Hungary at least two weeks after their second Sinopharm dose found that 90% under 50 years old developed protective antibodies. But the percentage declined with age, and 50% of those over 80 had none.
The study by two Hungarian researchers was posted online this week but not yet reviewed by other scientists. Three outside experts said they had no problems with the methodology of the study of the vaccine developed by Sinopharm’s Beijing Institute of Biological Products.
“This is very, very worrying that these people, who are high-risk, have a poor antibody response,” said Jin Dong-yan, a Hong Kong University virologist who was not affiliated with the study.
Antibody levels are not a direct measure of how protected a person is from COVID-19, but there is growing evidence that they are a good proxy. One expert cautioned that the choice of test kits could have limited the accuracy of the measurements.
Still, the study’s findings have value and are the first public, scientific attempt to analyze the effect of the Sinopharm vaccine in the elderly, said Wang Chenguang, a former professor at Peking Union Medical College and an immunology expert.
China’s National Health Commission declined to comment on the study, saying it would only respond to studies by governments or major research institutions.
This is not the first time questions have been raised about the efficacy of the vaccine, which was given a greenlight by the World Health Organization in May and is being used in more than 50 countries, many of which seized upon it when other vaccines were tough to come by.
A spokesperson for the WHO said Wednesday that its experts “are aware of the study and continue to look at all available evidence.”
The agency’s advisers raised questions months ago about whether it provided protection in people 60 and over, but when it was OK’d a WHO expert said that there was no reason to think it would work differently in the elderly.
The vaccine is one of two similar shots developed by Sinopharm. The state-owned Chinese company’s research showed that almost all the participants in final-stage clinical trials were under 60 – and its own researchers said there was insufficient evidence to say whether the vaccines work in the elderly. Overall, the Beijing Institute vaccine was found to be 78% effective.
In Hungary, concern about the shots led many to seek out private antibody tests. Eventually the capital city of Budapest offered free testing to elderly residents as part a bid to ratchet up pressure on the government to conduct its own wider survey and provide booster shots to those who need them.
After initially rebuffing calls for a government response to efficacy concerns – including from the antibody study’s authors Balazs Sarkadi and Tamas Ferenci – Prime Minster Viktor Orban finally acquiesced last week in the face of growing public anger. He announced that the government would provide its citizens with an optional third shot.
His office said, though, that all vaccines authorized by Hungary are effective.
The United Arab Emirates and Bahrain both announced in May that they, too, would offer a third dose of Sinopharm amid concerns about an insufficient antibody response. Bahrain recommended that people over 50 and some other vulnerable people receive Pfizer-BioNTech’s vaccine as their booster regardless of whether they got Sinopharm initially.
CNBG, the Sinopharm subsidiary that oversees the Beijing Institute, has said a third dose is not part of the company’s clinical guidance.
It’s not clear how many doses of the Beijing Institute Sinopharm vaccine have been exported. Overall, China exported 500 million vaccines doses in the first half of the year, and the company is one of country’s two major COVID vaccine makers, along with privately owned Sinovac.
The Global Alliance for Vaccines and Immunization recently ordered 550 million doses from the two companies for the U.N.-backed COVAX program.
Both Sinopharm vaccines are also in wide use in China, including in the elderly. The country’s National Health Commission said in April that the shots provide some protection, even though it acknowledged that early stages of clinical trials of Sinopharm’s vaccines and two others found fewer antibodies in people 60 and over.
In Budapest, Beata Englohner became concerned for her 76-year-old mother after hearing that people who had been vaccinated with Sinopharm were shown to have no antibodies.
Englohner started a Facebook group to press the government to address the issue. She is cautiously optimistic now that Hungary will offer a third dose.
“We’re very glad that we achieved our aim and that we were heard,” she said. “Though we’re a bit afraid that we’ll receive what we already got before.”
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Efficacy, Immunogenicity, and Safety of Vaccines Produced From Different COVID-19 Vaccine Platforms
Vaccine Efficacy
At present, most developers & manufacturers set the laboratory-confirmed COVID-19 as the primary endpoint for Phase 3 clinical trials, which is the most effective indicator to evaluate the protective efficacy of vaccines. At the end of 2020, protection data of 8 vaccines from 4 platforms have been published.
The efficacy of these vaccines, referred to as VE henceforth, ranges from 50.38% to 95%. Remarkable VEs of 95% for Pfizer mRNA vaccine, and 94.1% for Moderna mRNA vaccine have been reported (50, 51).
Adenovirus vectored vaccine Sputnik V, Ad26.COV2.S and Ad5-nCoV exhibited VE of 91.6%, 66% and 65.7%, respectively (52). Interestingly, AstraZeneca reported a 90% VE for its adenovirus vectored vaccine when a low dose prime, and standard dose boost regimen was employed, which went down to 62.1% for a standard dose prime and standard dose boost regimen of vaccination (53). The efficacy of Novavax recombinant subunit vaccine reported for the phase 3 clinical trial conducted in UK was 89.3% (54). while those for the inactivated vaccines of Sinopharm and Sinovac were 79.34% and 50.38%, respectively (55).
The following highlights emerge from the currently published VEs –
1) All reported VEs are higher than the 50% criterion required by WHO, FDA and EMA, indicating that the currently developed COVID-19 vaccines are efficacious against symptomatic COVID-19 in early stage (about 2-3 months) after vaccination (56–58). However, the long-term protective effect of the approved vaccines is currently unknown.
2) The VE reported for elderly population is relatively lower. This is concerning because the elderly are more susceptible to SARS-CoV-2 and show a higher death rate (59, 60). Most published data for current vaccines show relatively lower VE for the elderly (50, 53). Moderna mRNA vaccine showed a 95.6% VE for people younger than 65, but the VE dropped to 86.4% for people over 65. Pfizer mRNA vaccine showed a VE of 94.7% in the elderly population over 65, which is comparable to that observed in younger population (51).
3) The evidences for VE can be unreliable due to complicated demographic characteristics, such as population and geography. Exploratory subgroup analysis of BNT162b2 (Pfizer-BioNTech) showed a lower VE in Brazilian recipients (87.7%) than those in US (94.9%) and Argentinian recipients (97.2%) (51). The VE of CoronaVac (Sinovac) was reported as 91.25% in Turkey and 86% in UAE, respectively. While Brazil announced an overall 50.38% efficacy against COVID-19 for CoronaVac, and 78% against mild symptoms, which is far lower than that reported in Turkey (61). Above results indicate that the differences caused by population or geography do exist. AZD1222 (AstraZeneca) showed similar vaccine efficacy in SD/SD group in UK and Brazilian recipients, generalized from two diverse settings with different timings for the booster dose. The immunization interval between the two doses in the UK trial was mostly >12 weeks, while that in Brazil was less than 6 weeks. Interestingly, a significantly different efficacy of protection was exhibited by the first standard dose during immunization in the above two nations (71.2% in Brazil and 55% in UK). However, vaccine efficacy in UK recipients reached a comparable level with that in Brazil after the booster dose. Therefore, it is likely that a longer interval between the two doses of the vaccine might increase the immune protection (53).
4) VEs were affected by locally circulating variants. In the end of 2020, South Africa announced the emergency of a new variant B.1.351 (62, 63), and P.1 variant (64) was also found being prevalent in Brazil. Both variants contain mutations of E484K, K417T, and N501Y. E484K have been shown to reduce neutralization sensitivity of vaccine sera against SARS-CoV-2 (65, 66). NVX-CoV2373 developed by Novavax resulted in a point estimate of total VE of 89.3%, while 49.4% was reported in a Phase 2b clinical trial conducted in South Africa (67). Janssen’s vaccine Ad26.COV2.S resulted in 66% effective overall in preventing moderate to severe COVID-19, and reduced to 57% in South Africa (68). Recently, AstraZeneca-Oxford conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of ChAdOx1 nCoV-19 in South Africa, dedicating a VE of 21.9% overall and 10.4% against B.1.351 (31). Therefore, the circulating variants combined with geography factor greatly affect the calculated VE of vaccine candidates.
5) The dose and dosage influence the efficacy of the vaccine. The virus vectored vaccine is generally considered for application as a single-dose regimen to avoid compromising the immunogenicity of the second dose of the vaccine by the immune response against the viral vector elicited by the first dose. Although the AstraZeneca adenovirus vectored vaccine used a two-dose immunization regimen, the interim phase 3 clinical report showed that one standard dose provided similar protection as two standard doses regimen, with 55% (1 dose) and 60.3% (2 doses) VE in the UK recipients, and 71.2% (1 dose) and 64.2% (2 doses) VE in Brazilian recipients (53). Interestingly, cutting down half of the first dose of AZD1222 induced a protection of 90%, which was higher than the VE of 60.3% provided by two standard doses regimen in UK recipients. These statistics suggest that the adenovirus vaccine immunization schedule could be further optimized.
Reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071852/
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More information: Tamás Ferenci et al, Virus neutralizing antibody responses after two doses of BBIBP-CorV (Sinopharm, Beijing CNBG) vaccine, (2021). DOI: 10.1101/2021.07.15.21260362
