Immunogenicity and safety of boosting with a recombinant two-component SARS-CoV-2 vaccine: two randomized, parallel-controlled, phase 2 studies.

BACKGROUND: Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials. RESEARCH DESIGN AND METHODS: Study-1 involved subjects were randomized (1:1:1) to receive 20 µg ReCOV, 40 µg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 µg ReCOV (pilot batch, ReCOV HA), 20 µg ReCOV (commercial batch, ReCOV TC), or 30 µg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster. RESULTS: Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence. CONCLUSIONS: Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV's potential for enhanced protection, supported by strong cross-neutralization and immune persistence. CLINICAL TRIAL REGISTRATION: Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.

Safety and immunogenicity of multivalent SARS-CoV-2 protein vaccines: a randomized phase 3 trial.

Background: COVID-19 vaccines that offer broad-spectrum protection are needed. We aimed to evaluate the safety and immunogenicity of multivalent vaccines, SCTV01E and SCTV01C, and compare them with an inactivated vaccine. Methods: In the phase 3 trial (ClinicalTrials.gov: NCT05323461), adult participants previously vaccinated with Sinopharm's inactivated SARS-CoV-2 vaccine (BBBIP-CorV) were assigned to receive one booster dose of BBBIP-CorV, 20 µg SCTV01C, or 30 µg SCTV01E. The primary endpoint was to evaluate the geometric mean titers (GMT) of neutralizing antibody (nAb) against the Delta and Omicron BA.1 variants on day 28 after injection. Additional endpoints included GMTs of nAb against Delta (B.1.617.2) and Omicron BA.1 variants on day 180, GMTs against BA.5 on day 28, as well as solicited adverse events (AEs) within seven days, unsolicited AEs within 28 days, and serious AEs, AEs of special interest within 180 days after vaccination. Findings: Between May 30, 2022 and October 28, 2022, a total of 1351 participants were randomized to BBBIP-CorV, SCTV01C, or SCTV01E in a 1:1:1 ratio, with immunogenicity assessments performed on the first 300 participants. For BBBIP-CorV, SCTV01C, and SCTV01E groups, the day 28 GMTs of neutralizing antibody against Omicron BA.1 were a 2.38-, 19.37-, and 28.06-fold increase from baseline; the GMTs against Omicron BA.5 were 2.07-, 15.89- and 21.11-fold increases; the GMTs against Delta variants were 1.97-, 12.76-, and 15.88-fold increases, respectively. The day 28 geometric mean ratio (GMR) of SCTV01C/BBIBP-CorV for Omicron BA.1 was 6.49 (95% CI: 4.75, 8.88), while the GMR of SCTV01E/BBIBP-CorV was 9.56 (95% CI: 6.85, 13.33). For the Delta variant, the day 28 GMR of SCTV01C/BBIBP-CorV was 6.26 (95% CI: 4.78, 8.19), and the day 28 GMR of SCTV01E/BBIBP-CorV was 7.26 (95% CI: 5.51, 9.56). On Day 180, the GMTs against Omicron BA.1 were 2.80-, 9.51-, and 15.56-fold increase from baseline, while those against Delta were 1.58-, 5.49-, and 6.63-fold for BBBIP-CorV, SCTV01C, and SCTV01E groups, respectively. Subgroup analyses showed that SCTV01C and SCTV01E induced uniformly high GMTs against both BA.1 and BA.5, demonstrating its superiority over BBIBP-CorV, regardless of baseline GMT levels. Safety and reactogenicity were similar among the three vaccines. Most AEs were Grade 1 or 2. There were 15 ≥Grade 3 AEs: 6 in the BBIBP-CorV group, 4 in the SCTV01C group and 5 in the SCTV01E group. No SAE was reported and one grade 1 AESI (Bell's palsy) was observed in SCTV01C group. Interpretation: A booster dose of the tetravalent vaccine SCTV01E consistently induced high neutralizing antibody responses against Omicron BA.1, BA.5, and Delta variants, demonstrating superiority over inactivated vaccine. There is evidence to suggest that SCTV01E may have GMT superiority over bivalent vaccine SCTV01C against Delta, BA.1 and BA.5 variants. Funding: This study was sponsored by Sinocelltech Ltd., and funded by the Beijing Science and Technology Planning Project [Z221100007922012] and the National Key Research and Development Program of China [2022YFC0870600].

Safety and immunogenicity of a tetravalent and bivalent SARS-CoV-2 protein booster vaccine in men.

The safety and immunogenicity of a protein-based tetravalent vaccine SCTV01E that contains spike protein ectodomain (S-ECD) of Alpha, Beta, Delta and Omicron BA.1 are assessed and compared with bivalent protein vaccine SCTV01C (Alpha and Beta variants) and monovalent mRNA vaccine (NCT05323461). The primary endpoints are the geometric mean titers (GMT) of live virus neutralizing antibodies (nAb) to Delta (B.1.617.2) and Omicron BA.1 at day 28 post-injection. The secondary endpoints include the safety, day 180 GMTs against Delta and Omicron BA.1, day 28 GMTs to BA.5, and seroresponse rates of neutralizing antibodies and T cell responses at day 28 post-injection. 450 participants, comprising of 449 males and 1 female, with a median age (range) of 27 (18-62) years, are assigned to receive one booster dose of BNT162b2, 20 µg SCTV01C or 30 µg SCTV01E and completed 4-week follow-up. All SCTV01E related adverse events (AEs) are mild or moderate and no Grade ≥3 AE, serious AE or new safety concerns are identified. Day 28 GMT of live virus neutralizing antibodies and seroresponse against Omicron BA.1 and BA.5 with SCTV01E are significantly higher than those with SCTV01C and BNT162b2. These data indicate an overall neutralization superiority with tetravalent booster immunization in men.

Safety and immunogenicity of a bivalent SARS-CoV-2 protein booster vaccine, SCTV01C, in adults previously vaccinated with mRNA vaccine: a randomized, double-blind, placebo-controlled phase 1/2 clinical trial.

BACKGROUND: Booster vaccination is an efficient way to address the waning protection of vaccines and immune escape of SARS-CoV-2 variants. We aimed to assess the safety and immunogenicity of SCTV01C, a novel bivalent protein vaccine as a booster for people who previously received two doses of mRNA vaccine. METHODS: In this randomized, phase 1/2 trial, adults fully vaccinated with mRNA vaccines 3-24 month earlier were enrolled. Participants received SCTV01C at 20 µg, 40 µg or placebo. The primary endpoints were adverse reactions within 7 days and immunogenicity on Day 28 after vaccination. This trial was registered with ClinicalTrials.gov (NCT05043311). FINDINGS: Between January 27 and April 28, 2022, 234 adults were randomly assigned to receive SCTV01C or placebo. The most common solicited adverse events (AEs) were Grade 1 injection-site pain (10.7%) and pyrexia (6.3%). There were no reports of Grade 3 or above solicited AE, serious AEs or AEs of special interests. On Day 28 post the booster, the geometric mean concentrations (GMCs) of the specific binding IgG antibodies to spike protein for placebo, 20 µg and 40 µg SCTV01C were 1649, 4153 and 5354 BAU/mL, with fold of increase from baseline of 1.0, 2.8 and 3.4-fold, respectively. GMTs of neutralizing antibodies against live Delta variant were 1280, 3542, and 4112, with fold of increase of 1.1, 3.9 and 4.1-fold, respectively; GMTs of neutralizing antibodies against live Omicron variant were 218, 640, and 1083, with fold of increase of 1.1, 4.4 and 5.1-fold, respectively. Participants with low neutralizing antibody titers at baseline (below the lower limit of quantitation) had 64.0 and 49.4-fold of increase in GMTs for Delta and Omicron, respectively. INTERPRETATION: The heterologous booster of SCTV01C was safe, and induced uniformly high cross-neutralization antibody responses against Delta and Omicron variants. FUNDING: Beijing Science and Technology Plan Project (Z221100007922012) and the National Key Research and Development Program of China (2022YFC0870600) supported this study.

Emerging and distinct video head impulse test responses in elderly with vestibular symptoms.

INTRODUCTION: Dizziness has been reported to be the most common symptom in elderly population. Video head impulse test, VHIT, allows clinicians to assess the vestibular function in elderly individuals, during their initial stages of vestibular symptoms. Inferences from VHIT responses were traditionally low vestibulo-ocular reflex gain or a normal vestibulo-ocular reflex gain. However, the possibility of a third and new variant of the vestibulo-ocular reflex gain has not been clinically explored yet. OBJECTIVES: To determine and report distinct patterns of vestibulo-ocular reflex gain using VHIT in elderly individuals with vestibular symptoms. METHODS: Retrospective cross-sectional study was done on a group of elderly patients who were above 70 years of age. These individuals were subjected to VHIT during their symptomatic phase. A vestibulo-ocular reflex gain value between 0.80-01.20 (Horizontal plane) was considered normal. The gain above and below this cutoff range was considered abnormal. RESULTS: 39 elderly patients (15 males and 24 females) whose mean age range was 74.71 years were evaluated for the VHIT response. Vestibulo-ocular reflex gain obtained was categorized into three distinct patterns: (i) normal vestibulo-ocular reflex gain, (ii) reduced vestibulo- ocular reflex gain and (iii) increased vestibulo-ocular reflex gain. The mean vestibulo- ocular reflex gain for both left and right horizontal canals varied significantly between the three groups (p < 0.05). No significant effect of age and vestibulo-ocular reflex gain was noted, though vestibulo-ocular reflex gain was higher in 80 years and above age (p > 0.05). CONCLUSION: Elderly individuals with dizziness may show varying responses with vestibulo-ocular reflex gain during the symptomatic period. The third type of hyperactive vestibule-ocular reflex responses that emerged from the current study were potential indicators of fluid dynamic changes in the inner ear. These responses need to be explored further as it relates to new clinical markers for both peripheral and central vestibular disorders.

Emerging and distinct video head impulse test responses in elderly with vestibular symptoms / Respostas emergentes e distintas do teste do impulso cefálico por vídeo em idosos com sintomas vestibulares

Abstract Introduction Dizziness has been reported to be the most common symptom in elderly population. Video head impulse test, VHIT, allows clinicians to assess the vestibular function in elderly individuals, during their initial stages of vestibular symptoms. Inferences from VHIT responses were traditionally low vestibulo-ocular reflex gain or a normal vestibulo-ocular reflex gain. However, the possibility of a third and new variant of the vestibulo-ocular reflex gain has not been clinically explored yet. Objectives To determine and report distinct patterns of vestibulo-ocular reflex gain using VHIT in elderly individuals with vestibular symptoms. Methods Retrospective cross-sectional study was done on a group of elderly patients who were above 70 years of age. These individuals were subjected to VHIT during their symptomatic phase. A vestibulo-ocular reflex gain value between 0.80-01.20 (Horizontal plane) was considered normal. The gain above and below this cutoff range was considered abnormal. Results 39 elderly patients (15 males and 24 females) whose mean age range was 74.71 years were evaluated for the VHIT response. Vestibulo-ocular reflex gain obtained was categorized into three distinct patterns: (i) normal vestibulo-ocular reflex gain, (ii) reduced vestibulo- ocular reflex gain and (iii) increased vestibulo-ocular reflex gain. The mean vestibulo- ocular reflex gain for both left and right horizontal canals varied significantly between the three groups (p< 0.05). No significant effect of age and vestibulo-ocular reflex gain was noted, though vestibulo-ocular reflex gain was higher in 80 years and above age (p> 0.05). Conclusion Elderly individuals with dizziness may show varying responses with vestibulo-ocular reflex gain during the symptomatic period. The third type of hyperactive vestibule-ocular reflex responses that emerged from the current study were potential indicators of fluid dynamic changes in the inner ear. These responses need to be explored further as it relates to new clinical markers for both peripheral and central vestibular disorders.

Resumo Introdução Estima‐se que a tontura seja o sintoma mais comum na população idosa. O teste do impulso cefálico por vídeo, VHIT (do inglês Video Head Impulse Test), permite que os médicos avaliem a função vestibular em idosos, durante os estágios iniciais dos sintomas vestibulares. As inferências das respostas do VHIT tradicionalmente tem sido baixo ganho de reflexo vestíbulo‐ocular ou ganho normal do reflexo vestíbulo‐ocular. Entretanto, a possibilidade de uma terceira e nova variante de ganho do reflexo vestíbulo‐ocular ainda não foi explorada clinicamente. Objetivos Determinar e relatar padrões distintos de ganho do reflexo vestíbulo‐ocular com VHIT em idosos sintomáticos com sintomas vestibulares. Método Estudo transversal retrospectivo feito em um grupo de idosos com mais de 70 anos. Esses indivíduos foram submetidos ao VHIT durante a fase sintomática. Um valor de ganho do reflexo vestíbulo‐ocular entre 0,80 a 01,20 (plano horizontal) foi considerado normal. O ganho acima e abaixo dessa faixa de corte foi considerado anormal. Resultados Foram avaliados para a resposta do VHIT 39 idosos (15 homens e 24 mulheres) com média de 74,71 anos. O ganho do reflexo vestíbulo‐ocular obtido foi categorizado em três padrões: (i) ganho de reflexo vestíbulo‐ocular normal, (ii) ganho de reflexo vestíbulo‐ocular reduzido e (iii) ganho de reflexo vestíbulo‐ocular aumentado. O ganho médio do reflexo vestíbulo‐ocular para ambos os canais horizontais esquerdo e direito variou significativamente entre os três grupos (p < 0,05). Nenhum efeito significante da idade e ganho do reflexo vestíbulo‐ocular foi observado, embora o ganho do reflexo vestíbulo‐ocular fosse maior na idade de 80 anos e acima (p > 0,05). Conclusão Indivíduos idosos com tontura podem apresentar respostas variáveis com o ganho do reflexo vestíbulo‐ocular durante o período sintomático. O terceiro tipo de respostas hiperativas do reflexo vestíbulo‐ocular que emergiram do estudo atual foi indicador potencial de mudanças na dinâmica dos fluidos na orelha interna. Essas respostas precisam ser mais exploradas, pois podem estar relacionadas a novos marcadores clínicos para distúrbios vestibulares periféricos e centrais.