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PLoS Med ; 19(5): e1003991, 2022 05.
Article in English | MEDLINE | ID: covidwho-1846918


BACKGROUND: Emerging and future SARS-CoV-2 variants may jeopardize the effectiveness of vaccination campaigns. Therefore, it is important to know how the different vaccines perform against diverse SARS-CoV-2 variants. METHODS AND FINDINGS: In a prospective cohort of 165 SARS-CoV-2 naive health care workers in the Netherlands, vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S), we performed a head-to-head comparison of the ability of sera to recognize and neutralize SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma, Delta and Omicron). Repeated serum sampling was performed 5 times during a year (from January 2021 till January 2022), including before and after booster vaccination with BNT162b2. Four weeks after completing the initial vaccination series, SARS-CoV-2 wild-type neutralizing antibody titers were highest in recipients of mRNA-1273, followed by recipients of BNT162b2 (geometric mean titers (GMT) of 358 [95% CI 231-556] and 214 [95% CI 153-299], respectively; p<0.05), and substantially lower in those vaccinated with the adenovirus vector-based vaccines AZD1222 and Ad26.COV2.S (GMT of 18 [95% CI 11-30] and 14 [95% CI 8-25] IU/ml, respectively; p<0.001). VOCs neutralization was reduced in all vaccine groups, with the greatest reduction in neutralization GMT observed against the Omicron variant (fold change 0.03 [95% CI 0.02-0.04], p<0.001). The booster BNT162b2 vaccination increased neutralizing antibody titers for all groups with substantial improvement against the VOCs including the Omicron variant. We used linear regression and linear mixed model analysis. All results were adjusted for possible confounding of age and sex. Study limitations include the lack of cellular immunity data. CONCLUSIONS: Overall, this study shows that the mRNA vaccines appear superior to adenovirus vector-based vaccines in inducing neutralizing antibodies against VOCs four weeks after initial vaccination and after booster vaccination, which implies the use of mRNA vaccines for both initial and booster vaccination.

COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Cohort Studies , Health Personnel , Humans , Netherlands/epidemiology , Prospective Studies , SARS-CoV-2/genetics
Am J Respir Crit Care Med ; 205(5): 483-485, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1648827

COVID-19 , Humans , SARS-CoV-2
BMJ Open ; 12(1): e052752, 2022 01 06.
Article in English | MEDLINE | ID: covidwho-1613004


OBJECTIVES: It has been suggested that ethnic minorities have been disproportionally affected by the COVID-19. We aimed to determine whether prevalence and correlates of past SARS-CoV-2 exposure varied between six ethnic groups in Amsterdam, the Netherlands. DESIGN, SETTING, PARTICIPANTS: Participants aged 25-79 years enrolled in the Healthy Life in an Urban Setting population-based prospective cohort (n=16 889) were randomly selected within ethnic groups and invited to participate in a cross-sectional COVID-19 seroprevalence substudy. OUTCOME MEASURES: We tested participants for SARS-CoV-2-specific antibodies and collected information on SARS-CoV-2 exposures. We estimated prevalence and correlates of SARS-CoV-2 exposure within ethnic groups using survey-weighted logistic regression adjusting for age, sex and calendar time. RESULTS: Between 24 June and 9 October 2020, we included 2497 participants. Adjusted SARS-CoV-2 seroprevalence was comparable between ethnic Dutch (24/498; 5.1%, 95% CI 2.8% to 7.4%), South-Asian Surinamese (22/451; 4.9%, 95% CI 2.2% to 7.7%), African Surinamese (22/400; 8.3%, 95% CI 3.1% to 13.6%), Turkish (30/408; 7.9%, 95% CI 4.4% to 11.4%) and Moroccan (32/391; 7.2%, 95% CI 4.2% to 10.1%) participants, but higher among Ghanaians (95/327; 26.3%, 95% CI 18.5% to 34.0%). 57.1% of SARS-CoV-2-positive participants did not suspect or were unsure of being infected, which was lowest in African Surinamese (18.2%) and highest in Ghanaians (90.5%). Correlates of SARS-CoV-2 exposure varied across ethnic groups, while the most common correlate was having a household member suspected of infection. In Ghanaians, seropositivity was associated with older age, larger household sizes, living with small children, leaving home to work and attending religious services. CONCLUSIONS: No remarkable differences in SARS-CoV-2 seroprevalence were observed between the largest ethnic groups in Amsterdam after the first wave of infections. The higher infection seroprevalence observed among Ghanaians, which passed mostly unnoticed, warrants wider prevention efforts and opportunities for non-symptom-based testing.

COVID-19 , SARS-CoV-2 , Aged , Child , Cross-Sectional Studies , Ghana , Humans , Netherlands/epidemiology , Prevalence , Prospective Studies , Seroepidemiologic Studies
Cell Rep Med ; 3(1): 100486, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1569129


The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals.

Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , /immunology , COVID-19/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Vaccination/methods , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , COVID-19/virology , Female , Follow-Up Studies , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Neutralization Tests , Prospective Studies , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Treatment Outcome
Elife ; 102021 11 23.
Article in English | MEDLINE | ID: covidwho-1529013


Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11- to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2- to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 vaccination in macaques and humans, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.

COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Viral/blood , Coronavirus/immunology , Cross Reactions/immunology , Healthy Volunteers , Humans , Immunoglobulin G/immunology , Macaca , Middle East Respiratory Syndrome Coronavirus/immunology , Principal Component Analysis , Protein Domains/immunology , Serum/immunology , Serum/virology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Tetanus Toxoid/immunology , /immunology
EBioMedicine ; 72: 103589, 2021 10.
Article in English | MEDLINE | ID: covidwho-1433161


BACKGROUND: To optimise the use of available SARS-CoV-2 vaccines, some advocate delaying second vaccination for individuals infected within six months. We studied whether post-vaccination immune response is equally potent in individuals infected over six months prior to vaccination. METHODS: We tested serum IgG binding to SARS-CoV-2 spike protein and neutralising capacity in 110 healthcare workers, before and after both BNT162b2 messenger RNA (mRNA) vaccinations. We compared outcomes between participants with more recent infection (n = 18, median two months, IQR 2-3), with infection-vaccination interval over six months (n = 19, median nine months, IQR 9-10), and to those not previously infected (n = 73). FINDINGS: Both recently and earlier infected participants showed comparable humoral immune responses after a single mRNA vaccination, while exceeding those of previously uninfected persons after two vaccinations with 2.5 fold (p = 0.003) and 3.4 fold (p < 0.001) for binding antibody levels, and 6.4 and 7.2 fold for neutralisation titres, respectively (both p < 0.001). The second vaccine dose yielded no further substantial improvement of the humoral response in the previously infected participants (0.97 fold, p = 0.92), while it was associated with a 4 fold increase in antibody binding levels and 18 fold increase in neutralisation titres in previously uninfected participants (both p < 0.001). Adjustment for potential confounding of sex and age did not affect these findings. INTERPRETATION: Delaying the second vaccination in individuals infected up to ten months prior may constitute a more efficient use of limited vaccine supplies. FUNDING: Netherlands Organization for Health Research and Development ZonMw; Corona Research Fund Amsterdam UMC; Bill & Melinda Gates Foundation.

Antibodies, Viral/blood , Antibody Formation , COVID-19 Vaccines/pharmacology , COVID-19 , SARS-CoV-2/immunology , Adult , COVID-19 Vaccines/therapeutic use , Female , Health Personnel , Humans , Immunity, Humoral , Immunoglobulin G/blood , Male , Middle Aged , Netherlands , Prospective Studies , Time Factors , Treatment Outcome
Sci Adv ; 7(36): eabj5365, 2021 Sep 03.
Article in English | MEDLINE | ID: covidwho-1403006


Emerging SARS-CoV-2 variants of concern (VOCs) pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three VOCs (B.1.1.7, B.1.351, and P.1) in cohorts of COVID-19 convalescent patients (n = 69) and Pfizer-BioNTech vaccine recipients (n = 50). Spike binding and neutralization against all three VOCs were substantially reduced in most individuals, with the largest four- to sevenfold reduction in neutralization being observed against B.1.351. While hospitalized patients with COVID-19 and vaccinees maintained sufficient neutralizing titers against all three VOCs, 39% of nonhospitalized patients exhibited no detectable neutralization against B.1.351. Moreover, monoclonal neutralizing antibodies show sharp reductions in their binding kinetics and neutralizing potential to B.1.351 and P.1 but not to B.1.1.7. These data have implications for the degree to which pre-existing immunity can protect against subsequent infection with VOCs and informs policy makers of susceptibility to globally circulating SARS-CoV-2 VOCs.