COVID-19 vaccines in HK: Immunogenicity, AEFIs, nasal spray vaccine updates

Neutralizing antibody, anti-spike immunoglobulin G (IgG) and total antibody levels are higher in recipients of the mRNA coronavirus disease 2019 (COVID-19) vaccine vs inactivated COVID-19 vaccine, studies in healthcare workers (HCWs) in Hong Kong have shown.

HKU study: Comparative immunogenicity of vaccines

In a comparative study, researchers from the University of Hong Kong (HKU) collected blood samples from 1,442 HCWs recruited from public and private hospitals as well as medical clinics in Hong Kong. The blood samples, collected before vaccination, before the second dose of the mRNA or inactivated vaccine, and 21–35 days after the second dose, were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that bind to the receptor binding domain (RBD) of the spike protein, using an enzyme-linked immunosorbent assay (ELISA). ELISA-positive samples were tested for neutralizing antibodies using a surrogate virus neutralization (sVNT) assay, followed by a plaque reduction neutralization test (PRNT) with live SARS-CoV-2.  [Lancet Microbe 2021;doi:10.1016/S2666-5247(21)00177-4]

Preliminary results from 93 fully vaccinated HCWs with complete data (mRNA vaccine recipients: n=63; median age, 37 years; male, 55.6 percent) (inactivated vaccine recipients: n=30; median age, 47.6 years; male, 23.3 percent) showed substantial increases in antibody concentrations as measured by ELISA and sVNT assay after the first dose of the mRNA vaccine, which increased again after the second dose. In contrast, inactivated vaccine recipients had low antibody concentrations after the first dose and moderate antibody concentrations after the second dose.

In a subset of 12 HCWs in each group with PRNT results available, geometric mean PRNT₅₀ and PRNT₉₀ titres were 269 and 113, respectively, after the second dose of the mRNA vaccine. In comparison, much lower geometric mean PRNT₅₀ and PRNT₉₀ titres of 27 and 8.4, respectively, were observed after the second dose of the inactivated vaccine.

“Neutralizing antibody titres have been proposed as a correlate of protection for SARS-CoV-2 vaccines,” the researchers wrote. [Nat Med 2021;doi:10.1038/s41591-021-01377-8; Vaccines (Basel) 2021;9:238; Vaccine 2021;39:4423-4428] “The difference in concentrations of neutralizing antibodies identified in our study could translate into substantial differences in vaccine effectiveness.”

“Our study did not include data on other potential correlates of protection, such as T cells or antibody-dependent cellular cytotoxicity antibody. Future studies could investigate alternative strategies to increase antibody concentrations and clinical protection in recipients of inactivated vaccines, including administration of booster doses,” they added.

HKSH study: Serological response to vaccines

In another study, researchers from the Hong Kong Sanatorium & Hospital (HKSH) recruited 457 HCWs who enrolled for COVID-19 vaccination between 22 February and 30 April 2021. Serial measurements of anti-spike immunoglobulin M/immunoglobulin G (IgG)/total antibody and surrogate neutralizing antibody levels were performed after the first and second doses of the inactivated vaccine (at ≥26 days and ≥28 days, respectively) and mRNA vaccine (at ≥19 days and ≥28 days, respectively). [Hong Kong Med J 2021;doi:10.12809/hkmj219605]

The currently published study cohort included 220 (48.1 percent) HCWs who chose the inactivated vaccine and 237 (51.9 percent) who chose the mRNA vaccine based on personal preference. Those who chose the inactivated vaccine were significantly older (mean age, 49.11 years vs 44.06 years in the mRNA vaccine group; p<0.0001), with a significantly higher prevalence of medical comorbidities (31.6 percent vs 22.22 percent; p=0.0318). “At the time of writing, 210 HCWs have received two doses of the inactivated vaccine, while 92 have received two doses of the mRNA vaccine,” reported the researchers.

While significantly more mRNA vs inactivated vaccine recipients developed anti-spike IgG after the first dose (99.1 percent vs 64.7 percent; p<0.0001), anti-spike IgG positivity was achieved in a majority of HCWs after the second dose of either vaccine, with no significant difference between the groups (100 percent vs 99 percent; p=1).

However, the mRNA vaccine induced higher IgG and total antibody levels than the inactivated vaccine after both doses. Mean IgG and total antibody levels were 1,618.0 AU/mL vs 157.6 AU/mL and 104.2 U/mL vs 9.6 U/mL, respectively, after the first dose of the mRNA vs inactivated vaccine, and 11,572.6 AU/mL vs 1,005.2 AU/mL and 244.1 U/mL vs 141.7 U/mL, respectively, after the second dose (both p<0.0001).

After the second dose, rates of surrogate neutralizing antibody positivity were significantly higher among mRNA vs inactivated vaccine recipients (100 percent vs 94 percent; p<0.0194), as was surrogate neutralizing antibody levels (mean signal inhibition, 94.5 percent vs 66.7 percent; p<0.0001).

“Both vaccines are immunogenic in these HCWs. Our findings underscore the importance of maintaining social distancing and other infection control measures until 4 weeks after completing the two-dose regimen,” the researchers suggested.

“Although most vaccine recipients developed antibodies after the second dose, the level of antibody or neutralizing activity required to confer protection against future infection is currently not well defined,” they added. “More research is needed for better understanding of serology after vaccination. Data collection is ongoing and new findings will be published when available.”

AEs following immunization

“As of 30 May 2021, more than 3,000 reports of adverse events following immunization [AEFIs] had been received out of 2,364,000 doses of COVID-19 vaccines administered,” said Professor Ivan Hung of the LKS Faculty of Medicine, HKU, at a roundtable meeting of the Hong Kong College of Dermatologists (HKCD) held on 26 June 2021.

These included 1,787 AEFI reports (0.28 percent) out of 1,014,800 doses of the inactivated vaccine and 1,502 AEFI reports (0.11 percent) out of 1,349,200 doses of the mRNA vaccine administered.

The most frequently reported AEFIs were dizziness, chest discomfort, headache, rash and palpitation for the inactivated vaccine, and dizziness, headache, chest discomfort, rash and palpitation for the mRNA vaccine.

“A majority of hospitalizations for AEFIs were minor and self-limiting events,” said Hung.

Of 77 AEFI reports of Bell’s palsy received as of 30 May 2021, 38 and 39 were in recipients of the inactivated and mRNA vaccine, respectively. “Importantly, 90 percent of individuals with vaccine-related Bell’s palsy fully recovered, especially with early treatment,” said Hung. “The overall incidence of Bell’s palsy as an AEFI was lower than the annual baseline incidence.”

“[With regard to Bell’s palsy], the inactivated vaccine is of particular interest due to the timeframe association, [with event occurrence] within 48 hours,” Hung added. “This identified signal has been reported to the Department of Health and manufacturer of the inactivated vaccine, with a suggestion that Bell’s palsy be added to the vaccine’s package insert.”

Among 21 death cases reported as of 30 May 2021, six were deemed to have no causal relationship and 15 were preliminarily considered to have no association with COVID-19 vaccination.

Nasal spray vaccine updates

As of 21 July 2021, 5.01 million doses of COVID-19 vaccines had been administered in Hong Kong, with 2.09 million individuals (27.9 percent of the population) having been fully vaccinated.

At HKU, researchers have developed a nasal spray vaccine that is currently being evaluated in a phase I, randomized, double-blind, placebo-controlled, dose-escalation and dose-expansion clinical trial. The vaccine, known as DelNS1-nCoV-RBD LAIV, is made from a genetically engineered live attenuated influenza virus that expresses the RBD of SARS-CoV-2’s spike protein. In the phase I trial estimated to enroll 115 healthy adults aged 18–55 years, the HKU researchers will evaluate the cumulative incidence of reactogenicity in all study participants who have received at least one dose of the vaccine, and the seroconversion rate for serum RBD-specific binding antibodies for all participants who have received two doses of the vaccine, given 4 weeks apart. [NCT04809389]

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