Monday, April 12, 2021

Preprint: Increased Breakthrough Rates of SARS-CoV-2 VOC in BNT162b2 (Pfizer) mRNA Vaccinated Individuals



Between the often egregious headlines, and the `spin' being offered by some on social media, you could be forgiven for waking up this morning believing that a major study published over the weekend showed that the Pfizer/BioNTech mRNA COVID vaccine is more or less useless against the South African variant.

The Israeli study, while interesting, is limited by its small size (400 vaccinated & 400 unvaccinated carriers), and the low incidence of B.1.351 in Israel during the study period.  Data on VOC B.1.1.7 was more robust, and therefore more reliable.

 The authors explained how they selected candidates for this study:

We focused on vaccinated carriers, divided into two categories: (a) individuals who had a positive PCR test that was performed between 14 days after the 1st dose and a week after the 2nd dose (denoted as partial effectiveness, PE), and (b) individuals who had a positive PCR test that was performed at least one week after the second vaccine dose (denoted as full effectiveness, FE)
Each vaccinee (case) was matched with an unvaccinated carrier (control) with similar demographic characteristics (date of PCR, age, sex, ethnic sector, and geographic location) to reduce bias associated with differential exposure (Methods).

Each carrier underwent sequencing to determine the COVID variant they were carrying. The authors wrote:

When examining the results, it became evident that B.1.1.7 was the predominant strain of virus in Israel over the entire sampling period, increasing in frequency over time (Fig. 1A). Conversely, the B.1.351 strain was at an overall frequency of less than 1% in our sample, confirming previous reports (Fig. 1B) [14]. No other variants of concern or variants of interests, as defined by the WHO, were found in our sample (Fig. S2).

The low incidence (< 1%) of VOC B.1.351 makes it impossible to assign statistical significance to their findings, but the authors suggest the vaccine - at least in the first few weeks - is likely less effective against the South African variant than the WT COVID. 

There is better data regarding B.1.1.7, and here, they found that one dose of the Pfizer vaccine had reduced effectiveness against the UK variant, but that improved markedly 7 days after the second dose. 

The authors cautioned:

The main caveat of our study was the small sample size of both the WT and B.1.351 variants. These small samples sizes are a product of (a) the dramatic increase in frequency of the B.1.1.7 variant (first detected in Israel in mid-December 2020) (Fig. 1A), and (b) the low frequency of the B.1.351 variant in Israel [14].
In fact, in our latest samples obtained in late February and early March 2021, we noted fixation of the B.1.1.7 variant, but this interpretation requires caution as our sample size was low (Fig. 1A). Furthermore, caution is required from over-interpreting the odds ratios obtained, as the absolute numbers we found, in particular for B.1.351 infections, are very small.

In other words, this study can't tell us - one way or the other - how effective the Pfizer vaccine is against the South African variant.  It suggests, but doesn't quantify, lower effectiveness.   And given some of the earlier laboratory studies we've seen, that would not be unexpected. 

What this study does suggest is that one shot of the mRNA COVID vaccine - at least in the first few weeks - may not protect as well against some VOCs as it reportedly does against the wild type (WT) virus.  

A finding the countries that have opted for a delayed 2nd dose may want to consider.

First, the link and abstract from the study, followed by an excerpt from the discussion.  Follow the link to read the full preprintI'll have a brief postscript when you return. 

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals

Talia Kustin, Noam Harel, Uriah Finkel, Shay Perchik, Sheri Harari, Maayan Tahor, Itamar Caspi, Rachel Levy, Michael Leschinsky, Shifra Ken Dror, Galit Bergerzon, Hala Gadban, Faten Gadban, Eti Eliassian, Orit Shimron, Loulou Saleh, Haim Ben-Zvi, Doron Amichay, Anat Ben-Dor, Dana Sagas, Merav Strauss, Yonat Shemer Avni, Amit Huppert, Eldad Kepten, Ran D. Balicer, Doron Nezer, Shay Ben-Shachar, Adi Stern


The SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines.

Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. Here, we performed a case-control study that examined whether BNT162b2 vaccinees with documented SARS-CoV-2 infection were more likely to become infected with B.1.1.7 or B.1.351 compared with unvaccinated individuals.

Vaccinees infected at least a week after the second dose were disproportionally infected with B.1.351 (odds ratio of 8:1). Those infected between two weeks after the first dose and one week after the second dose, were disproportionately infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs under different dosage/timing conditions. 

Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high against B.1.1.7, among those fully vaccinated. These results overall suggest that vaccine breakthrough infection is more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.



From a biological point of view, the breakthrough cases observed in this study might either be due to immune evasion of both strains, or the ability of B.1.17 to create higher viral loads [3]. Given the low frequency of B.1.351 across time (Fig. 1A) [14], our results overall suggest that selection does not strongly favour the B.1.351 variant in the particular conditions in Israel.

In view of this low frequency of B.1.351 (across all groups of study herein, including the FE category; Fig. 1B), we suggest that there may be higher rates of vaccine breakthrough with B.1.351, but it is possible that (a) vaccine effectiveness coupled with enacted nonpharmaceutical interventions remain sufficient to prevent its spread, and/or (b) B.1.1.7 outcompetes B.1.351, possibly due to its high transmission rate [3]. Our results emphasize the importance of tracking viral variants in a rigorous framework and of increasing vaccination, which we conclude is the safest and most effective means of preventing the onwards spread of B.1.351 and other possible future VOCs.

(Continue . . . )

Concerns that B.1.351 (or P.1 or any of the other variants) might partially evade the current vaccine are nothing new.  In fact, its been a major topic of discussion in this blog for months. 

Less than two weeks ago (see NIH Announces Clinical Trial For Moderna COVID-19 Variant (B.1.351) Vaccine), we looked at efforts to create and test new vaccines designed to combat the South African VOC.  

It would not be unreasonable to expect that in order to control COVID, and manage its emerging variants, we'll be forced to created and dispense updated vaccines for years to come.  While perhaps not the best case scenario, it beats not having a vaccine option at all.