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

Abstract

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.

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

“…We previously showed that the levels of ACE2‐blocking Abs declined from 4 to 12 weeks after a single dose and thereby possibly increasing the susceptibility to infection by 16 weeks. 5 However, 73.9% still had detectable ACE2‐blocking Abs, while robust T and B cell memory responses were seen in >90% at 16 weeks. 5 Although there are no data regarding the efficacy of a single dose of the vaccine in preventing infection at ≥16 weeks, we found that 12.5% of this cohort with a longer dosing gap had been infected with the virus, with mildly symptomatic or asymptomatic infection.…”

“… 5 However, 73.9% still had detectable ACE2‐blocking Abs, while robust T and B cell memory responses were seen in >90% at 16 weeks. 5 Although there are no data regarding the efficacy of a single dose of the vaccine in preventing infection at ≥16 weeks, we found that 12.5% of this cohort with a longer dosing gap had been infected with the virus, with mildly symptomatic or asymptomatic infection. This is not surprising as Sri Lanka had a high number of cases from April to June due to the alpha variant 25 and even a higher number of cases with the delta variant from June to the end of September due to the delta variant.…”

“…2 However, many countries increased the dosing gap to 16 weeks to administer a single dose to a larger population 3,4 and also due to the delay in obtaining adequate vaccines for administering the second dose on time. 5 It was later shown that an increase in the gap between the two doses beyond 12 weeks, and even up to 45 weeks, resulted in higher antibody titers after the second dose of the vaccine. 6 AZD1222 was the first vaccine to be rolled out in Sri Lanka, with the immunization of the health care workers.…”

“…We showed that at ≥16 weeks postimmunization with a single dose of AZD1222, 93.7% of those >70 years had SARS‐CoV‐2‐specific antibodies, although ACE2 receptor‐blocking antibodies (those that correlate with neutralizing antibodies) was significantly less in those >60 years of age. 5 However, robust memory T cell and B cell responses were seen in over 90% of individuals. Although it has been shown that an increase in the gap between the two doses subsequently led to higher antibody titers, 6 there are limited data in the differences in dosing gaps on antibody responses to SARS‐CoV‐2 variants of concern (VOCs), differences in antibody responses in different age groups as well as with those with comorbidities, and also the influence of the dosing gap on T cell responses.…”

A quest for universal anti-SARS-CoV-2 T cell assay: systematic review, meta-analysis, and experimental validation

“…In order to bring homogeneity in the readouts of ELISPOT datasets, we only focused to examine studies on COVID-19 vaccines that had received WHO EUL (Emergency Use Listing), and had demonstrated their effectiveness in real-world settings. Based on these criteria, we obtained 19 datasets from 6 research articles 34 , 35 , 42 – 44 , 51 in which S1 peptide pool was used for stimulation and 8 datasets from 6 research articles 34 , 41 , 42 , 46 – 48 used whole spike peptide pool for stimulation. The range of readouts of ELISPOT for the studies using S1 antigen was found to be 35–550, 10–119, 75–180 SFUs/million for ChAdOx1 nCoV-19, BNT162b2, and Sinopharm, respectively.…”