Perspectives and gaps in the management of food allergy and anaphylaxis in the Asia-Pacific Region.

Background: Food allergy (FA), which is a condition that has no effective cure and can result in severe life-threatening allergic reactions, remains a global public health concern; however, little is known about how FAs are currently managed in the Asia-Pacific region. Objective: The main objective of this survey was to evaluate the epidemiology of FA, as well as the availability of resources and practices for management of FA and anaphylaxis by health care providers across Asia. Methods: From June 2022 to September 2022, a questionnaire-based survey comprising 66 questions was electronically sent to member societies of the Asia Pacific Association of Allergy Asthma and Clinical Immunology by using Survey Monkey. Results: A total of 20 responses were received from 15 member countries and territories. Compared with the pediatric data, there was a lack of prevalence data for FA in adults. Except for Australia and Japan, most regions had between 0.1 and 0.5 allergists per 100,000 population and some had fewer than 0.1 allergists per 100,000 population. The perceived rate of FA in regions with a short supply of allergists was high. Although specific IgE tests and oral food challenges were available in all regions, the median wait time for oral food challenges at government facilities was 37 days (interquartile range = 10.5-60 days). Seven regions still relied on prescriptions of ampules and syringes of injectable adrenaline, and adrenaline autoinjectors were not accessible in 4 regions. Oral immunotherapy as FA treatment was available in half of the surveyed countries and territories. Conclusions: Our study offers a cross-sectional evaluation of the management practices for FA in each Asia Pacific Association of Allergy Asthma and Clinical Immunology member country or territory. Urgent actions are required to enhance allergy services, improve the accessibility and affordability of adrenaline autoinjectors, and conduct robust epidemiologic studies.

Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals.

As there are limited data on B-cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron, and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine. Using overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n = 30), WT infected (n = 30), delta infected (n = 30), omicron infected + vaccinated (n = 20) and Sinopharm (BBIBP-CorV) vaccinees (n = 30). We then investigated the sensitivity and specificity of these immunodominant regions and analyzed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses, and bat Sarbecoviruses. We identified four immunodominant regions aa 29-52, aa 155-178, aa 274-297, and aa 365-388, which were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines.

Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals.

Background: As there are limited data on B cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine. Methods: Using overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n=30), WT infected (n=30), delta infected (n=30), omicron infected+vaccinated (n=20) and Sinopharm (BBIBP-CorV) vaccinees (n=30). We then investigated the sensitivity and specificity of these immunodominant regions and analysed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses and bat Sarbecoviruses. We then investigated the kinetics of responses to these regions in those with varying severity of acute COVID-19. Results: We identified four immunodominant regions aa 29-52, aa 155-178, aa 274 to 297 and aa 365 to 388, were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, with WT infected individuals predominantly recognizing aa155 to 178 regions, delta infected individuals and vaccinated+omicron infected individuals predominantly recognizing regions aa 29 to 52 and aa 274 to 294 regions. Sinopharm vaccinees recognized all four regions, with the magnitude of responses significantly lower than other groups. >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses. Conclusions: N-protein specific responses appear to be detectable in over 90% of those who were naturally infected or vaccinated with a whole virus inactivated vaccine, with responses mainly directed against four regions of the protein, which were highly conserved. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines.

Comparison of the kinetics and magnitude of antibody responses to different SARS-CoV-2 proteins in Sinopharm/BBIBP-CorV vaccinees following the BNT162b2 booster or natural infection.

The kinetics and magnitude of antibody responses to different proteins of the SARS-CoV-2 virus in Sinopharm/BBIBP-CorV vaccinees has not been previously studied. Therefore, we investigated antibody responses to different SARS-CoV-2 proteins at 2 weeks, 3 months, and 6 months post-second dose in previously infected (n = 20) and uninfected (n = 20) Sinopharm/BBIBP-CorV vaccinees. The IgG antibodies to the S, S1 and S2 and N were several folds higher in those who had natural infection compared to uninfected individuals at all time points. We then compared the persistence of antibody responses and effect of natural omicron infection or BNT162b2 booster in Sinopharm/BBIBP-CorV vaccinees. We measured the total antibodies to the RBD, ACE2 blocking antibodies and antibody responses to different SARS-CoV-2 proteins in Sinopharm vaccinees at 7 months post second dose, including those who remained uninfected and not boosted (n = 21), or those who had previous infection and who did not obtain the booster (n = 17), those who were not infected, but who received a BNT162b2 booster (n = 30), or those who did not receive the booster but were infected with omicron (n = 29). At 7 months post second dose uninfected (no booster) had the lowest antibody levels to the RBD, while omicron infected vaccinees showed significantly higher anti-RBD antibody levels (p = 0.04) than vaccinees who received the booster. Only 3/21 cohort A (14.3%) had ACE2 blocking antibodies, while higher frequencies were observed in naturally infected individuals (100%), those who received the booster (18/21, 85.7%), and omicron infected individuals (100%). Pre-vaccination, naturally infected had the highest antibody levels to the N protein. These data suggest that those previously infected Sinopharm/BBIBP-CorV vaccinees have a robust antibody response, 7 months post vaccination, while vaccinees who were naturally infected with omicron had a similar immune response to those who received the booster. It will be important to investigate implications for subsequent clinical protection.

Immune responses to Sinopharm/BBIBP-CorV in individuals in Sri Lanka.

As there are limited data of the immunogenicity of the Sinopharm/BBIBP-CorV in different populations, antibody responses against different SARS-CoV-2 variants of concern and T cell responses, we investigated the immunogenicity of the vaccine, in individuals in Sri Lanka. SARS-CoV-2-specific antibodies were measured in 282 individuals who were seronegative at baseline, and ACE2 receptor blocking antibodies, antibodies to the receptor-binding domain (RBD) of the wild-type (WT), alpha, beta and delta variants, ex vivo and cultured IFNγ ELISpot assays, intracellular cytokine secretion assays and B cell ELISpot assays were carried out in a sub cohort of the vaccinees at 4 and 6 weeks (2 weeks after the second dose). Ninety-five percent of the vaccinees seroconverted, although the seroconversion rates were significantly lower (p < 0.001) in individuals >60 years (93.3%) compared to those who were 20-39 years (98.9%); 81.25% had ACE2 receptor blocking antibodies at 6 weeks, and there was no difference in these antibody titres in vaccine sera compared to convalescent sera (p = 0.44). Vaccinees had significantly less (p < 0.0001) antibodies to the RBD of WT and alpha, although there was no difference in antibodies to the RBD of beta and delta compared to convalescent sera; 27.7% of 46.4% of vaccinees had ex vivo IFNγ and cultured ELISpot responses respectively, and IFNγ and CD107a responses were detected by flow cytometry. Sinopharm/BBIBP-CorV appeared to induce a similar level of antibody responses against ACE2 receptor, delta and beta as seen following natural infection.

Comparison of the immunogenicity of five COVID-19 vaccines in Sri Lanka.

To determine the antibody responses elicited by different vaccines against SARS-CoV-2, we compared antibody responses in individuals 3 months post-vaccination in those who had received different vaccines in Sri Lanka. Abs to the receptor binding domain (RBD) of the ancestral (wild type) virus (WT) as well as to variants of concern (VoCs), and ACE2 blocking Abs, were assessed in individuals vaccinated with Moderna (n = 225), Sputnik V (n = 128) or Sputnik light (n = 184) and the results were compared with previously reported data on Sinopharm and AZD1222 vaccinees. A total of 99.5% of Moderna, >94% of AZD1222 or Sputnik V and >70% of Sputnik light, >60% of Sinopharm vaccine recipients, had a positive response to ACE2 blocking antibodies. The ACE2 blocking antibody levels were highest to lowest was Moderna > Sputnik V/AZD1222 (had equal levels) > Sputnik light > Sinopharm. All Moderna recipients had antibodies to the RBD of WT, alpha and beta, while positivity rates for delta variant was 80%. The positivity rates for Sputnik V vaccinees for the WT and VoCs were higher than for AZD1222 vaccinees while those who received Sinopharm had the lowest positivity rates (<16.7%). The total antibodies to the RBD were highest for the Sputnik V and AZD1222 vaccinees. The Moderna vaccine elicited the highest ACE2 blocking antibody levels followed by Sputnik V/AZD1222, while those who received Sinopharm had the lowest levels. These findings highlight the need for further studies to understand the effects on clinical outcomes.

Persistence of immune responses to the Sinopharm/BBIBP-CorV vaccine.

BACKGROUND: To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP-CorV, we investigated immune responses in a cohort of Sri Lankan individuals. METHODS: SARS-CoV-2 specific total antibodies were measured in 20-39 years (n = 61), 40-59 years (n = 120) and those >60 years of age (n = 22) by enzyme-linked immunosorbent assay, 12 weeks after the second dose of the vaccine. Angiotensin-converting enzyme 2 (ACE2) receptor blocking antibodies (ACE2R-Ab), antibodies to the receptor-binding domain (RBD) of the ancestral virus (WT) and variants of concern, were measured in a sub cohort. T cell responses and memory B cell responses were assessed by ELISpot assays. RESULTS: A total of 193/203 (95.07%) of individuals had detectable SARS-CoV-2 specific total antibodies, while 67/110 (60.9%) had ACE2R-Ab. A total of 14.3%-16.7% individuals in the 20-39 age groups had detectable antibodies to the RBD of the WT and variants of concern, while the positivity rates of those ≥60 years of age was <10%. A total of 14/49 (28.6%) had Interferon gamma ELISpot responses to overlapping peptides of the spike protein, while memory B cell responses were detected in 9/20 to the S1 recombinant protein. The total antibody levels and ACE2R-Ab declined from 2 to 12 weeks from the second dose, while ex vivo T cell responses remained unchanged. The decline in ACE2R-Ab levels was significant among the 40-59 (p = .0007) and ≥60 (p = .005) age groups. CONCLUSIONS: Antibody responses declined in all age groups, especially in those ≥60 years, while T cell responses persisted. The effect of waning of immunity on hospitalization and severe disease should be assessed by long term efficacy studies.

Kinetics of immune responses to SARS-CoV-2 proteins in individuals with varying severity of infection and following a single dose of the AZD1222.

To characterize the IgG and IgA responses to different SARS-CoV-2 proteins, we investigated the antibody responses to SARS-CoV-2 following natural infection and following a single dose of AZD1222 (Covishield), in Sri Lankan individuals. The IgG and IgA responses were assessed to S1, S2, RBD, and N proteins in patients at 4 weeks and 12 weeks since the onset of illness or following vaccination. Antibodies to the receptor-binding domain of SARS-CoV-2 wild type (WT), α, ß, and λ and ACE2 (Angiotensin Converting Enzyme 2) receptor blocking antibodies were also assessed in these cohorts. For those with mild illness and in vaccines, the IgG responses to S1, S2, RBD, and N protein increased from 4 weeks to 12 weeks, while it remained unchanged in those with moderate/severe illness. In the vaccines, IgG antibodies to the S2 subunit had the highest significant rise (P < 0.0001). Vaccines had several-fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with natural infection. At 12 weeks, the haemagglutination test (HAT) titres were significantly lower to the α in vaccines and significantly lower in those with mild illness and in vaccines to ß and for λ. No such difference was seen in those with moderate/severe illness. Vaccines had significantly less IgA to SARS-CoV-2, but comparable IgG responses those with natural infection. However, following a single dose vaccines had reduced antibody levels to the VOCs, which further declined with time, suggesting the need to reduce the gap between the two doses, in countries experiencing outbreaks due to VOCs.

Kinetics of immune responses to the AZD1222/Covishield vaccine with varying dose intervals in Sri Lankan individuals.

BACKGROUND: To understand the kinetics of immune responses with different dosing gaps of the AZD1222 vaccine, we compared antibody and T cell responses in two cohorts with two different dosing gaps. METHODS: Antibodies to the SARS-CoV-2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled 12 weeks post second dose (cohort 1) and in 77 individuals with a median dosing gap of 21.4 weeks (cohort 2) sampled 6 weeks post second dose. ACE2-blocking antibodies (ACE2-blocking Abs), antibodies to the receptor-binding domain (RBD) of  variants of concern (VOC), and ex vivo T cell responses were assessed in a subcohort. RESULTS: All individuals (100%) had SARS-CoV-2-specific total antibodies and 94.2% of cohort 1 and 97.1% of cohort 2 had ACE2-blocking Abs. There was no difference in antibody titers or positivity rates in different age groups in both cohorts. The ACE2-blocking Abs (p < .0001) and antibodies to the RBD of the VOCs were significantly higher in cohort 2 compared to cohort 1. 41.2% to 65.8% of different age groups gave a positive response by the hemagglutination assay to the RBD of the ancestral virus and VOCs in cohort 1, while 53.6%-90% gave a positive response in cohort 2. 17/57 (29.8%) of cohort 1 and 17/29 (58.6%) of cohort 2 had ex vivo interferon (IFN)γ ELISpot responses above the positive threshold. The ACE2-blocking antibodies (Spearman's r = .46, p = .008) and ex vivo IFNγ responses (Spearman's r = .71, p < .0001) at 12 weeks post first dose, significantly correlated with levels 12 weeks post second dose. CONCLUSIONS: Both dosing schedules resulted in high antibody and T cell responses post vaccination, although those with a longer dosing gap had a higher magnitude of responses, possibly as immune responses were measured 6 weeks post second dose compared to 12 weeks post second dose.

Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac).

As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018). 82.6% developed ACE2 receptor blocking antibodies, although levels were significantly lower than following natural infection (p = 0.0009) and a single dose of AZD1222 (p < 0.0001). Similar titres of antibodies were observed to the receptor binding domain of WT, B.1.1.7 and B.1.617.2 compared to AZD1222, while the levels for B.1.351 were significantly higher (p = 0.006) for Gam-COVID-Vac. 30% developed ex vivo IFNγ ELISpot responses (significantly lower than AZD1222), and high frequency of CD107a expressing T cells along with memory B cell responses. Although single dose of Gam-COVID-Vac was highly immunogenic, administration of a second dose is likely to be beneficial.

Antibody responses to Sinopharm/BBIBP-CorV in pregnant mothers in Sri Lanka.

BACKGROUND: There are limited data regarding the safety and immunogenicity of the Sinopharm/BBIBP-CorV vaccine in pregnancy. Therefore, we sought to investigate the antibody responses and maternal and fetal adverse events following this vaccine in pregnant mothers in Sri Lanka. METHODS AND FINDINGS: SARS-CoV-2 receptor binding domain (RBD) specific total antibodies and ACE2 blocking antibodies were measured by ELISA in pregnant mothers (n = 94) who received the vaccine in the first (n = 2), second (n = 57) and third (n = 33) trimester of pregnancy. Data regarding adverse events and fetal and maternal outcomes were obtained from the women once they delivered. No adverse maternal or fetal complications reported such as miscarriage, thrombotic events, hypertensive disorders, fetal death, preterm delivery, or congenital anomalies were reported. 58/94 (61.7%) had RBD binding antibodies and were found to be seropositive at the time of recruitment. All women seroconverted after the second dose and 31/36 previously uninfected women and 57/58 previously infected women gave a positive response to ACE2 blocking antibodies. The RBD binding antibody levels (p = 0.0002) and ACE2 blocking antibodies (p<0.0001) were significantly higher in previously infected individuals post-second dose compared to uninfected individuals. CONCLUSIONS: The Sinopharm/ BBIBP-CorV vaccine appeared safe and induced high seroconversion rates and ACE2 blocking antibodies in pregnant mothers in the second and third trimester in pregnancy. However, the RBD binding antibodies and ACE2 blocking antibodies post-second dose were significantly higher in previously infected pregnant mothers post-second dose, suggesting that two doses of the vaccine are likely to be less immunogenic in previously unexposed individuals.

Seroprevalence of SARS-CoV-2 Infection in the Colombo Municipality Region, Sri Lanka.

Background: As the Municipality Council area in Colombo (CMC) experienced the highest number of cases until the end of January 2021, in Sri Lanka, we carried out a serosurvey prior to initiation of the vaccination program to understand the extent of the SARS-CoV-2 outbreak. Methods: SARS-CoV-2 seropositivity was determined in 2,547 individuals between the ages of 10-86 years, by the Wantai total antibody ELISA. We also compared seroprevalence using the haemagglutination test (HAT) to evaluate its usefulness in carrying out serosurveys. Results: The overall seropositivity rate was 24.46%, while seropositivity by HAT was 18.90%. Although The SARS-CoV-2 infection detection rates by PCR were highest in the population between the ages of 20-60 years of age, there was no statistically significant difference in the seropositivity rates in different age groups. For instance, although the seropositivity rate was highest in the 10-20 age group (34.03%), the PCR positivity rate was 9.80%. Differences in the PCR positivity rates and seropositivity rates were also seen in 60-70-year-olds (8.90 vs. 30.4%) and in individuals >70 years (4.10 vs. 1.20%). The seropositivity rate of the females was 29.70% (290/976), which was significantly higher (p < 0.002) than in males 21.2% (333/1,571). Conclusions: A high seroprevalence rate (24.5%) was seen in all age groups in the CMC suggesting that a high level of transmission was seen during this time. The higher PCR positivity rates between the ages of 20-60 are likely to be due to increased testing carried out in the working population. Therefore, the PCR positivity rates, appear to underestimate the true extent of the outbreak and the age groups which were infected.

Kinetics of immune responses to the AZD1222/Covishield vaccine with varying dose intervals in Sri Lankan individuals.

BACKGROUND: To understand the kinetics of immune responses with different dosing gaps of the AZD1222 vaccine, we compared antibody and T cell responses in two cohorts with two different dosing gaps. METHODS: Antibodies to the SARS-CoV-2 virus were assessed in 297 individuals with a dosing gap of 12 weeks, sampled at 12 weeks post second dose (cohort 1) and in 77 individuals with a median dosing gap of 21.4 weeks (cohort 2) sampled 6 weeks post second dose. ACE2 receptor blocking antibodies (ACE2R-Abs), antibodies to the receptor binding domain (RBD) of the virus and variants of concern (VOC) and ex vivo T cell responses were assessed in a sub cohort. RESULTS: All individuals (100%) had SARS-CoV-2 specific total antibodies and 94.2% of cohort 1 and 97.1% of cohort 2 had ACE2R-blocking Abs. There was no difference in antibody titres or positivity rates in different age groups in both cohorts. The ACE2R-blocking Abs (p<0.0001) and antibodies to the RBD of the VOCs were significantly higher in cohort 2, compared to cohort 1. 41.2% to 65.8% of different age groups gave a positive response by the haemagglutination assay to the RBD of the ancestral virus and VOCs in cohort 1, while 53.6% to 90% gave a positive response in cohort 2. 17/57 (29.8%) of cohort 1 and 17/29 (58.6%) of cohort 2 had ex vivo IFNγ ELISpot responses above the positive threshold. The ACE2R-blocking antibodies and ex vivo IFNγ ELISpot responses at 12 weeks post-first dose, significantly correlated with levels 12 weeks post second dose (Spearman's r=0.46, p=0.008) and (Spearman's r=0.71, p<0.0001) respectively. CONCLUSIONS: Both dosing schedules resulted in high levels of antibody and T cell responses post vaccination, although those with a longer dosing gap had a higher magnitude of responses, possibly as immune responses were measured 6 weeks post second dose compared to 12 weeks post second dose.

Immune Responses to a Single Dose of the AZD1222/Covishield Vaccine at 16 Weeks in Individuals in Sri Lanka.

Due to limited access to vaccines, many countries have only administered a single dose of the AZD1222, whereas the dosage intervals have increased ≥4 wk. We sought to investigate the immunogenicity of a single dose of vaccine at ≥16 wk postimmunization. Severe acute respiratory syndrome coronavirus 2-specific Abs in 553 individuals and Abs to the receptor-binding domain of the Wuhan virus (wild-type) and the variants of concern, angiotensin-converting enzyme 2 receptor blocking Abs ex vivo and cultured IFN-γ T cell (Homo sapiens) responses and B cell (H. sapiens) ELISPOT responses, were investigated in a subcohort. The seropositivity rates in those >70 y of age (93.7%) was not significantly different compared with other age groups (97.7-98.2; Pearson χ2 = 7.8; p = 0.05). The Ab titers (Ab index) significantly declined (p < 0.0001) with increase in age. A total of 18 of 69 (26.1%) of individuals did not have angiotensin-converting enzyme 2 receptor-blocking Abs, whereas responses to the receptor-binding domain of wild-type (p = 0.03), B.1.1.7 (p = 0.04), and B.1.617.2 (p = 0.02) were significantly lower in those who were >60 y. Ex vivo IFN-γ T cell ELISPOT responses were seen in 10 of 66 (15.1%), whereas only a few expressed CD107a. However, >85% had a high frequency of cultured IFN-γ T cell ELISPOT responses and B cell ELISPOTs. Virus-specific Abs were maintained at ≥16 wk after receiving a single dose of AZD1222, although levels were lower to variants of concern, especially in older individuals. A single dose induced a high frequency of memory T and B cell responses.

Persistence of antibody and T cell responses to the Sinopharm/BBIBP-CorV vaccine in Sri Lankan individuals.

BACKGROUND: To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP-CorV, we investigated immune responses in a cohort of Sri Lankan individuals. METHODS: SARS-CoV-2 specific total antibodies were measured in 20-to-39 year (n=61), 40-to-59-year and those >60 years of age (n=22) by ELISA, 12 weeks after the second dose of the vaccine. ACE2 receptor blocking antibodies (ACE2R-Ab), antibodies to the receptor binding domain (RBD) of the ancestral virus (WT) and variants of concern, were measured in a sub cohort. T cell responses and memory B cell responses were assessed by ELISpot assays. RESULTS: 193/203 (95.07%) of individuals had detectable SARS-CoV-2 specific total antibodies, while 67/110 (60.9%) had ACE2R-Ab. 14.3% to 16.7% individuals in the 20 to 39 age groups had detectable antibodies to the RBD of the WT and VOC, while the positivity rates of those >60 years of age was <10%. 14/49 (28.6%) had IFN γ ELISpot responses to overlapping peptides of the spike protein, while memory B cell responses were detected in 9/20 to the S1 recombinant protein. The total antibody levels and ACE2R-Ab declined after 2 to 12 weeks from the second dose, while ex vivo T cell responses remained unchanged. The decline in ACE2R-Ab levels was significant among the 40 to 59 (p=0.0007) and ≥60 (p=0.005) age groups. CONCLUSIONS: Antibody responses declined in all age groups, especially in those >60 years, while T cell responses persisted. The effect of waning of immunity on hospitalization and severe disease should be assessed by long term efficacy studies.

Immune responses to a single dose of the AZD1222/Covishield vaccine in health care workers.

Several COVID-19 vaccines have received emergency approval. Here we assess the immunogenicity of a single dose of the AZD1222 vaccine, at one month, in a cohort of health care workers (HCWs) (629 naïve and 26 previously infected). 93.4% of naïve HCWs seroconverted, irrespective of age and gender. Haemagglutination test for antibodies to the receptor binding domain (RBD), surrogate neutralization assay (sVNT) and ex vivo IFNγ ELISpot assays were carried out in a sub-cohort. ACE2 blocking antibodies (measured by sVNT) were detected in 67/69 (97.1%) of naïve HCWs. Antibody levels to the RBD of the wild-type virus were higher than to RBD of B.1.1.7, and titres to B.1.351 were very low. Ex vivo T cell responses were observed in 30.8% to 61.7% in naïve HCWs. Previously infected HCWs, developed significantly higher (p < 0.0001) ACE2 blocking antibodies and antibodies to the RBD for the variants B.1.1.7 and B.1.351. This study shows high seroconversion after one vaccine dose, but also suggests that one vaccine dose may be insufficient to protect against emerging variants.