A retrospective study of the safety and immunogenicity of MVC-COV1901 vaccine for people living with HIV (preprint)

Safety and immunogenicity of MVC-COV1901, a recombinant COVID-19 protein vaccine, containing S-2P protein adjuvanted with CpG 1018 and aluminium hydroxide, was assessed for people living with HIV (PWH). A total of 57 PWH of ≥ 20 years of age who are on stable antiretroviral therapy were compared with 882 HIV-negative participants. Participants received 2 doses of MVC-COV1901 28 days apart. No vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in PWH and comparators, respectively, 28 days after second dose. After adjusting for sex, age, BMI category, and comorbidity, the adjusted GMT ratio of comparator/PWH was 3.2 (95% CI 2.5-4). A higher CD4/CD8 ratio was associated with a higher GMT (R = 0.27, p = 0.039). MVC-COV1901 has shown robust safety but elicited weaker immune responses in PWH. As a result, a third dose or booster doses of MVC-COV1901 may be appropriate for PWH. ClinicalTrials.gov registration: NCT04695652.

Titers and capacity of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: a single-blinded, randomized clinical trial (preprint)

Background Booster vaccination is important because of waning immunity and variant immune evasion. We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19. Methods and findings HCW at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2, half-dose mRNA-1273, mRNA-1273, and MVC-COV1901. The primary outcomes were humoral and cellular immunogenicity and the secondary outcomes safety and reactogenicity 28 days post-booster. 340 HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine. Anti-spike IgG increased by a fold of 8.4 for MCV-COV1901, 32.2 for BNT162b2, 47.6 for half-dose mRNA-1273 and 63.2 for mRNA1273. The live virus microneutralization assay (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron variant were 6.4 to 13.5 times lower than those against the wild type. Serum neutralizing antibody against omicron variant was undetectable in 60% of the participants who received MCV-COV1901 as a booster by LVMNA. By using pseudovirus neutralizing assay, we found that neutralization activity in the four groups against omicron variant were 4.6 to 5.2 times lower than that against the D614G. All booster vaccines induced comparable T cell response. Conclusions Third dose booster not only increases neutralizing antibody titer but also enhances antibody capacity against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those after primary series of ChAdOx1 nCov-19.

Safety and Immunogenicity of SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901 in People Living with HIV (preprint)

ObjectivesTo provide data on the immune response to COVID-19 vaccines in people living with HIV (PWH), MVC-COV1901, a recombinant protein vaccine containing S-2P protein adjuvanted with CpG 1018 and aluminium hydroxide, was assessed. MethodsA total of 57 PWH of [≥] 20 years of age who are on stable antiretroviral therapy and with CD4+ T cell [≥] 350 cells/mm3 and HIV viral load < 103 copies/ml were compared with 882 HIV-negative participants. Participants received 2 doses of MVC-COV1901 28 days apart. Safety and the immunogenicity were evaluated. ResultsNo vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in people living with HIV (PWH) and comparators, respectively, 28 days after second dose. The geometric mean titers (GMTs) (95% confidence interval [CI]) against wild type SARS-CoV-2 virus were 136.62 IU/mL (WHO Standardized International Unit) (95% CI 114.3-163.3) and 440.41 IU/mL (95% CI 421.3-460.4), for PWH and control groups, respectively, after adjusting for sex, age, BMI category, and comorbidity, and the adjusted GMT ratio of comparator/PWH was 3.22 (95% CI 2.6-4.1). A higher CD4/CD8 ratio was associated with a higher GMT (R=0.27, p=0.039). ConclusionsMVC-COV1901 has shown robust safety but weaker immunogenicity responses in PWH. As a result, a third dose or booster doses of MVC-COV1901 may be appropriate for PWH.

Relative COVID-19 viral persistence and antibody kinetics (preprint)

ImportanceThe COVID-19 antibody response is a critical indicator for evaluating immunity and also serves as the knowledge base for vaccine development. The picture is still not clear because of many limitations including testing tools, time of sampling, and the unclear impact of varying clinical status. In addition to these problems, antibody levels may not be equivalent to protective capacity. ObjectiveTo define the key factor for the different patterns of COVID-19 antibody response. DesignWe elucidated the antibody response with time-series throat and serum samples for viral loads and antibody levels, then used a neutralization test to evaluate protectiveness. SettingA medical center that typically cares for patients with moderate to severe diseases. Because of the low prevalence of COVID-19 in Taiwan and local government policy, however, we also admit COVID-19 patients with mild disease or even those without symptoms for inpatient care. ParticipantsRT-PCR-confirmed COVID-19 patients. ResultsWe found that only patients with relative persistence of virus at pharynx displayed strong antibody responses that were proportional to the pharyngeal viral load. They also had proportional neutralization titers per unit of serum. Although antibody levels decreased around 2 weeks after symptom onset, the neutralization efficacy per unit antibody remained steady and even continued to increase over time. The antibody response in patients with rapid virus clearance was weak, but the neutralization efficacy per unit antibody in these patients was comparable to those with persistent presence of virus. The deceased were with higher viral load, higher level of antibody, and higher neutralization titers in the serum, but the neutralization capacity per unit antibody is relatively low. Conclusions and RelevanceStrong antibody response depends on the relative persistence of the virus, instead of the absolute virus amount. The antibody response is still weak if large amount of virus is cleared quickly. The neutralization efficacy per unit antibody is comparable between high and low antibody patterns. Strong antibody response contains more inefficient and maybe even harmful antibodies. Low antibody response is also equipped with a capable B cell pool of efficient antibodies, which may expand with next virus encounter and confer protection. Key pointsO_ST_ABSQuestionC_ST_ABSThe key factor for the different "patterns" of COVID-19 antibody response. FindingsStrong antibody response depends on the relative persistence of the virus, instead of the absolute virus amount. The antibody response is still weak if large amount of virus is cleared quickly. The neutralization efficacy per unit antibody is comparable between high and low antibody patterns. High antibody level contains more inefficient antibodies. MeaningStrong response contains inefficient and maybe harmful antibodies. Low antibody response is also equipped with a capable B cell pool of efficient antibodies, which may expand with next virus encounter and confer protection.