Three-dose vaccination-induced immune responses protect against SARS-CoV-2 Omicron BA.2: a population-based study in Hong Kong.

Background: The ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the model city of universal masking of the world, has resulted in a major public health crisis. Although the third vaccination resulted in strong boosting of neutralization antibody, vaccine efficacy and correlate of immune protection against the major circulating Omicron BA.2 remain to be investigated. Methods: We investigated the vaccine efficacy against the Omicron BA.2 breakthrough infection among 470 public servants who had received different SARS-CoV-2 vaccine regimens including two-dose BNT162b2 (2 × BNT, n = 169), three-dose BNT162b2 (3 × BNT, n = 168), two-dose CoronaVac (2 × CorV, n = 34), three-dose CoronaVac (3 × CorV, n = 67) and third-dose BNT162b2 following 2 × CorV (2 × CorV+1BNT, n = 32). Humoral and cellular immune responses after three-dose vaccination were further characterized and correlated with clinical characteristics of BA.2 infection. Findings: During the BA.2 outbreak, 27.7% vaccinees were infected. The timely third-dose vaccination provided significant protection with lower incidence rates of breakthrough infections (2 × BNT 46.2% vs 3 × BNT 13.1%, p < 0.0001; 2 × CorV 44.1% vs 3 × CorV 19.4%, p = 0.003). Investigation of immune responses on blood samples derived from 90 subjects in three-dose vaccination cohorts collected before the BA.2 outbreak revealed that the third-dose vaccination activated spike (S)-specific memory B cells and Omicron cross-reactive T cell responses, which correlated with reduced frequencies of breakthrough infections and disease severity rather than with types of vaccines. Moreover, the frequency of S-specific activated memory B cells was significantly lower in infected vaccinees than uninfected vaccinees before vaccine-breakthrough infection whereas IFN-γ+ CD4 T cells were negatively associated with age and viral clearance time. Critically, BA.2 breakthrough infection boosted cross-reactive memory B cells with enhanced cross-neutralizing antibodies to Omicron sublineages, including BA.2.12.1 and BA.4/5, in all vaccinees tested. Interpretation: Our results imply that the timely third vaccination and immune responses are likely required for vaccine-mediated protection against Omicron BA.2 pandemic. Although BA.2 conferred the highest neutralization resistance compared with variants of concern tested before the emergence of BA.2.12.1 and BA.4/5, the third dose vaccination-activated S-specific memory B cells and Omicron cross-reactive T cell responses contributed to reduced frequencies of breakthrough infection and disease severity. Neutralizing antibody potency enhanced by BA.2 breakthrough infection in vaccinees with prior 3 doses of CoronaVac or BNT162b2 may reduce the risk of infection against ongoing BA.2.12.1 and BA.4/5. Funding: Hong Kong Research Grants Council Collaborative Research Fund, Health and Medical Research Fund, Wellcome Trust, Shenzhen Science and Technology Program, the Health@InnoHK, Innovation and Technology Commission of Hong Kong, China, National Program on Key Research Project, Emergency Key Program of Guangzhou Laboratory, donations from the Friends of Hope Education Fund and the Hong Kong Theme-Based Research Scheme.

Effectiveness of influenza vaccination in institutionalized older adults: a systematic review.

INTRODUCTION: Influenza infection is common among institutionalized older adults. Many nonrandomized observational studies on influenza vaccination suggested that it could reduce influenza-related hospitalizations and mortality in institutionalized older adults. Criticism regarding the effectiveness of influenza vaccine estimated by nonrandomized observational studies include the frailty selection bias and use of nonspecific outcome, such as all-cause mortality. METHODS: We conducted a systematic review of studies of influenza vaccination in institutionalized older adults to determine the effects on clinical outcomes. We searched for studies from 3 databases from 1946 to June 2013 assessing effectiveness against influenza infection. We selected studies with good comparability between vaccine group and control group. We expressed vaccine effectiveness (VE) as a proportion, using the formula VE = 1-relative risk or 1-odds ratio. We focused on the following outcomes: influenza-like illness (ILI), laboratory confirmed influenza, hospitalizations due to ILI, or pneumonia and death due to influenza or pneumonia. We did not include all-cause mortality. RESULTS: Eleven studies that satisfied the inclusion criteria were identified, representing 11,262 institutionalized older adults. After meta-analysis, we found a significant reduction in pneumonia (VE: 37%, 95% confidence interval [CI]: 18%-53%, P = .001) and death due to pneumonia or influenza (VE: 34%, CI: 10%-53%, P = .01). There was no significant heterogeneity between studies. There was no significant publication bias. CONCLUSION: Influenza vaccination in institutionalized older adults could reduce pneumonia and death due to pneumonia or influenza. Influenza vaccination is recommended for institutionalized older adults.

Efficacy of trivalent seasonal influenza vaccination in reducing mortality and hospitalization in Chinese nursing home older adults.

OBJECTIVE: To examine the clinical efficacy of the trivalent seasonal influenza vaccination among Chinese older adults residing in a nursing home. DESIGN: A 12-month prospective cohort study. Participants were divided into 2 groups based on their own choice on vaccination of trivalent seasonal influenza vaccine: vaccinated group and unvaccinated group. SETTING: Fifty-eight nursing homes in Hong Kong. PARTICIPANTS: A total of 1859 older adults residing in a nursing home. MEASUREMENTS: All-cause mortality, pneumonia-related mortality, all-cause hospitalization, and pneumonia-related hospitalization. RESULTS: A total of 1859 older adults residing in a nursing home were included: 1214 (65.3%) in the vaccinated group and 645 (34.7%) in the unvaccinated group. At 12 months of study, for all-cause mortality, 14.6% (177 of 1214) of the vaccinated group and 20.2% (130 of 645) of the unvaccinated group had died (P < .001). Multivariate analysis showed the hazard ratio for the vaccinated group was 0.72 (95% confidence interval [CI]: 0.54-0.95; P < .01). For pneumonia-related mortality, 9.4% (114 of 1214) of the vaccinated group and 12.7% (82 of 645) of the unvaccinated group died (P = .033). Multivariate analysis showed the hazard ratio for the vaccinated group was 0.80 (CI: 0.62-0.98; P < .05). The median number of all-cause hospitalizations per 1000 person-months was 55 (0-111) for the vaccinated group and 55 (0-167) for the unvaccinated group (P < .01). The median number of pneumonia-related hospitalizations per 1000 person-months was 0 (0-55) for the vaccinated group and 0 (0-111) for the unvaccinated group (P < .01). CONCLUSIONS: Vaccination of trivalent seasonal influenza vaccine in Chinese nursing home older adults significantly reduced all-cause and pneumonia-related mortality and hospitalization.

Human H7N9 avian influenza virus infection: a review and pandemic risk assessment.

China is undergoing a recent outbreak of a novel H7N9 avian influenza virus (nH7N9) infection that has thus far involved 132 human patients, including 37 deaths. The nH7N9 virus is a reassortant virus originating from the H7N3, H7N9 and H9N2 avian influenza viruses. nH7N9 isolated from humans contains features related to adaptation to humans, including a Q226L mutation in the hemagglutinin cleavage site and E627K and D701N mutations in the PB2 protein. Live poultry markets provide an environment for the emergence, spread and maintenance of nH7N9 as well as for the selection of mutants that facilitate nH7N9 binding to and replication in the human upper respiratory tract. Innate immune suppression conferred by the internal genes of H9N2 may contribute to the virulence of nH7N9. The quail may serve as the intermediate host during the adaptation of avian influenza viruses from domestic waterfowl to gallinaceous poultry, such as chickens and related terrestrial-based species, due to the selection of viral mutants with a short neuraminidase stalk. Infections in chickens, common quails, red-legged partridges and turkeys may select for mutants with human receptor specificity. Infection in Ratitae species may lead to the selection of PB2-E627K and PB2-D701N mutants and the conversion of nH7N9 to a highly pathogenic avian influenza virus.

Erratum: Human H7N9 avian influenza virus infection: a review and pandemic risk assessment.

[This corrects the article DOI: 10.1038/emi.2013.48.].