COVID-19 vaccine booster efficacy: What do new HK data show?

A booster dose of the mRNA-based BNT162b2 vaccine provides more robust antibody responses to SARS-CoV-2, including the Omicron BA.1 and BA.2 variants, than the inactivated CZ02 vaccine, but three doses of either vaccine are equally effective in reducing the risk of severe or fatal COVID-19, according to new local data presented at the 26th Hong Kong Medical Forum (HKMF).

Also presented at HKMF were updates on the intranasal COVID-19 vaccine developed by the University of Hong Kong (HKU), as well as new data from the US suggesting that COVID-19 vaccination is protective against post-acute sequelae of COVID-19 (PASC) symptoms, new-onset health conditions, and mortality.

“BNT162b2, being more immunogenic for humoral response, offers better short-term protection against infection as a booster dose than CZ02,” said Professor David Hui of the Department of Medicine & Therapeutics, Chinese University of Hong Kong (CUHK), at HKMF.

In a study by HKU and CUHK, a BNT162b2 booster dose elicited a 50 percent plaque reduction neutralization test (PRNT₅₀) titre ≥25.6 (ie, threshold for 50 percent protection from infection) against Omicron BA.1 in 88 percent of individuals who had received two doses of BNT162b2 and 80 percent of those who had received two doses of CZ02. However, only 3 percent of previously infected individuals and 3 percent of individuals who received three doses of CZ02 met this protective threshold. [Nat Med 2022;28:486-489]

“In previously infected individuals, levels of neutralizing antibodies against Omicron BA.1 were much higher after one dose of BNT162b2 vs CZ02,” said Hui.

When tested against Omicron BA.2, the researchers found much higher neutralizing antibody levels in individuals who received three doses of BNT162b2 vs three doses of CZ02 (geometric mean [GMT] of PRNT₅₀ antibody titre, 95.1 vs 9.3), while a booster dose of BNT162b2 after two doses of CZ02 also yielded a good level of neutralizing antibodies (GMT of PRNT₅₀ antibody titre, 46.0). [Euro Surveill 2022;doi:10.2807/1560-7917.ES.2022.27.18.2200178]

“However, individuals who had recovered from wild-type SARS-CoV-2 infection had no protection against Omicron BA.2 [GMT of PRNT₅₀ antibody titre, 9.0]. These individuals developed higher antibody levels against Omicron BA.2 after receiving one dose of BNT162b2 vs CZ02 [GMT of PRNT₅₀ antibody titre, 144.2 vs 28.3],” pointed out Hui.

“In unvaccinated individuals, Omicron infection induced only very weak antibody responses, which reacted with Omicron only. In contrast, a breakthrough infection caused by Omicron in individuals fully vaccinated with BNT162b2 led to a more potent antibody response … [,which] was broadly reactive and could neutralize other variants of concern [VOCs], such as Beta and Delta,” he continued.

Other studies by CUHK and HKU also showed that a BNT162b2 booster dose elicited higher levels of neutralizing antibodies to different VOCs, including Beta, Gamma, Delta and Omicron, than a CZ02 booster. [Am J Respir Crit Care Med 2022;205:844-847; Vaccines (Basel) 2022;10:160]

“While BNT162b2 is associated with better anti–spike immunoglobulin G [IgG], anti–receptor binding domain IgG and spike-associated T-cell responses than CZ02, CZ02 offers additional nucleocapsid protein–associated T-cell response that is not present in BNT162b2,” said Professor Ivan Hung of the Department of Medicine, HKU, at HKMF. [Clin Microbiol Infect 2022;28:410-418]

In terms of vaccine effectiveness (VE), a HKU study showed that three doses of BNT162b2 provided greater protection against mild or moderate COVID-19 than three doses of CZ02 in individuals aged 20–60 years (71.5 percent vs 42.3 percent) and those aged ≥60 years (71.6 percent vs 50.7 percent). [medRxiv 2022;doi:10.1101/2022.03.22.22272769]

“However, three doses of either BNT162b2 or CZ02 offered very high and comparable protection against severe or fatal COVID-19 in both age groups [VE, 98.5 percent vs 98.5 percent for age 20–60 years, 98.0 percent vs 97.9 percent for age ≥60 years],” said Hung.

“The intranasal COVID-19 vaccine [ie, DelNS1-nCoV-RBD LAIV] developed by HKU is currently being evaluated as a booster in a phase II trial. This will hopefully provide more robust mucosal immunity to protect against transmission,” Hung added.

A phase I trial of the intranasal vaccine has demonstrated safety and effective mucosal immunoglobulin immunity with good T-cell response in 115 adults aged 18–55 years. The results will be published shortly. [NCT04809389]

Meanwhile, the Centre of Health Protection now recommends a fourth dose of COVID-19 vaccine in older adults aged ≥60 years, uninfected adults 18–59 years of age at higher risk of COVID-19 exposure or with personal needs who have received the third dose >6 months ago, and those ≥12 years of age with immunocompromised conditions. Emerging VE data from Israel support the use of a fourth dose of BNT162b2 to maintain protection in individuals aged ≥60 years. [N Engl J Med 2022;386:1603-1614; medRxiv 2022;doi:10.1101/2022.03.24.22272835]

In addition to protection against COVID-19, a study in 1,578,719 patients with confirmed COVID-19 in the US showed that COVID-19 vaccination is also protective against PASC symptoms (including respiratory symptoms, headache, fatigue, body ache, and diarrhoea or constipation), new-onset health conditions (including hypertension, diabetes, thyroid disease, heart disease, malignant neoplasms, thrombosis, rheumatoid arthritis, and mental disorders), and mortality, compared with no vaccination. [Open Forum Infect Dis 2022;doi:10.1093/ofid/ofac228]

“Vaccination rates need to be ramped up, especially in the high-risk groups. Additional doses of current, adapted, or novel COVID-19 vaccines will be needed in the future to maintain high levels of protection against subsequent waves of SARS-CoV-2 caused by Omicron or future variants with similar escape potential,” Hui suggested.

Prof David Hui (left), Prof Ivan Hung (right)