Understanding influencing attributes of COVID-19 vaccine preference and willingness-to-pay among Chinese and American middle-aged and elderly adults: A discrete choice experiment and propensity score matching study.

Background and objective: COVID-19 has imposed burdens on public health systems globally. Owing to the urgency of vaccination, this study aimed at comparing the differences in preference and willingness to pay of COVID-19 vaccine among Chinese and American middle-aged and elderly adults. Methods: A cross-sectional survey containing demographic questions, rating their acceptance of COVID-19 vaccination with and without recommendations from friends, family members or employers (the social cues referred to in our study), and a discrete choice experiment understanding COVID-19 vaccine preference and willingness to pay was conducted to collect data. Propensity score matching was utilized to adjust confounding factors of baseline characteristics and the relative importance of respondents' preference for each attribute and its level was estimated using a conditional logit model. Then, willingness to pay was calculated. Results: In total, 3,494 (2,311 and 1,183 from China and the United States, respectively) completed the questionnaire, among which 3,444 questionnaires were effective. After propensity score matching, 1,604 respondents with 802 from the US and 802 from China were included. Under the influence of the social cues, Chinese respondents' vaccine acceptance decreased from 71.70 to 70.70%, while American respondents' vaccine acceptance increased from 74.69 to 75.81%. The discrete choice experiment showed that American respondents regarded the efficacy of COVID-19 vaccine as the most important attribute, whereas Chinese respondents attached the highest importance to the cost of vaccination. But overall, the COVID-19 vaccine with the higher efficacy, the milder adverse effect, the lower cost, and the longer duration will promote the preference of the public in both countries. Additionally, the public were willing to spend the most money for a reduction in COVID-19 vaccine adverse effect from moderate to very mild (37.476USD for the United States, 140.503USD for China), followed by paying for the 1% improvement in its efficacy and paying for the one-month extension of its duration. Conclusion: Given the impact of social cues on vaccine acceptance, Chinese government should promote reasonable vaccine-related information to improve national vaccination acceptance. Meanwhile, considering the influence of COVID-19 attributes on public preference and willingness to pay, regulating the vaccine pricing, improving the efficacy of the vaccine, reducing its adverse effect, and prolonging the duration of the vaccine works will contribute to vaccine uptake.

A broad and potent neutralization epitope in SARS-related coronaviruses.

Many neutralizing antibodies (nAbs) elicited to ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through natural infection and vaccination have reduced effectiveness to SARS-CoV-2 variants. Here, we show that therapeutic antibody ADG20 is able to neutralize SARS-CoV-2 variants of concern (VOCs) including Omicron (B.1.1.529) as well as other SARS-related coronaviruses. We delineate the structural basis of this relatively escape-resistant epitope that extends from one end of the receptor binding site (RBS) into the highly conserved CR3022 site. ADG20 can then benefit from high potency through direct competition with ACE2 in the more variable RBS and interaction with the more highly conserved CR3022 site. Importantly, antibodies that are able to target this site generally neutralize a broad range of VOCs, albeit with reduced potency against Omicron. Thus, this conserved and vulnerable site can be exploited for the design of universal vaccines and therapeutic antibodies.

SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. In this study, serum of Beta-infected patients revealed reduced cross-neutralization of wild-type virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wild type-elicited antibodies, including a public VH1-58 clonotype that targets the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift, with implications for design of next-generation vaccines and therapeutics.

Structural basis of a shared antibody response to SARS-CoV-2.

Molecular understanding of neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could accelerate vaccine design and drug discovery. We analyzed 294 anti-SARS-CoV-2 antibodies and found that immunoglobulin G heavy-chain variable region 3-53 (IGHV3-53) is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein. Co-crystal structures of two IGHV3-53-neutralizing antibodies with RBD, with or without Fab CR3022, at 2.33- to 3.20-angstrom resolution revealed that the germline-encoded residues dominate recognition of the angiotensin I converting enzyme 2 (ACE2)-binding site. This binding mode limits the IGHV3-53 antibodies to short complementarity-determining region H3 loops but accommodates light-chain diversity. These IGHV3-53 antibodies show minimal affinity maturation and high potency, which is promising for vaccine design. Knowledge of these structural motifs and binding mode should facilitate the design of antigens that elicit this type of neutralizing response.