Thread by @bencowling88

New preprint (not yet peer reviewed) on our randomized trial of third doses in HK, where BNT162b2 (BioNTech/Fosun Pharma/Pfizer) and CoronaVac (Sinovac) are the two available vaccines. With @nancyleung_hk @gmleunghku @svalko3 and others. Short thread(1/14)
medrxiv.org/content/10.110…

Among adults ≥18y who initially received two doses of CoronaVac, we randomized 101 to a CoronaVac booster (“CC-C”) and 118 to a BNT162b2 booster (“CC-B”). Among adults ≥18 who initially received BNT162b2, we randomized 118 to “BB-C” and 114 to “BB-B” (2/14)

The third doses were given at least 6 months after the second dose, and on average participants received the third dose about 7 months after their second dose (3/14)

We aimed to study antibody responses, T cell responses, and reactogenicity to the vaccine. When we planned the study we had not anticipated a large COVID epidemic occurring in the community, but a large epidemic did occur, allowing us to assess relative efficacy (4/14)

We measured antibody responses using a surrogate neutralization assay (sVNT) in all participants, and a live virus neutralization assay (PRNT50) in our high-biosecurity laboratory in a random subset of 20 participants per group (5/14)

Antibody responses against the ancestral virus (vaccine strain) and Omicron BA1 and BA2 were much stronger in recipients of third doses of BNT162b2, with very low levels of antibody against BA.2 in the BB-C and CC-C arms particularly in the live virus neutralization assay (6/14)

T-cell responses on day 7 were notable in the CC-C and CC-B arms, i.e. those primed with CoronaVac, and comparable between those two groups, but interestingly were not seen in the BB-C or BB-B arms (7/14)

Reactions to the vaccine were much stronger on average for recipients of a BNT162b2 booster, with the lowest rate of reactions reported in the BB-C arm (8/14)

Hong Kong experienced a very large epidemic of Omicron BA.2 in March 2022, with more than a million confirmed cases (14% of pop) and likely more than 50% of the population infected, with many infections not laboratory-confirmed and reported to govt (9/14)
wwwnc.cdc.gov/eid/article/28…

We identified 58 infections in total (13% of participants), including some infections that likely would not have been identified and reported to the govt if participants had not been in our study, so the 13% in our study can't be directly compared to 14% in the population (10/14)

We observed similar levels of infection in each of the four arms in the study, despite the substantial difference that we found in neutralizing antibodies (much higher in BNT162b2 recipients) (11/14)

Our study shows that regardless of whether individuals first received BNT162b2 or CoronaVac, they could choose either vaccine for a third dose (12/14)

Perhaps most interesting observations for us were (1) the weaker T cell responses to a third dose in those primed with BNT162b2, and (2) the disparity between neutralizing antibodies (much higher with BNT162b2 booster) versus vaccine efficacy (seems similar between arms) (13/14)

To rephrase the last point, we might need to look beyond neutralizing antibodies to find other immune markers that reflect the protection provided by CoronaVac(?) Our next step is to look at non-neutralizing antibodies to internal virus genes (14/14)