The novel mRNA vaccines of Moderna and Pfizer/BioNTech are among the most effective of all the developed vaccines at preventing infection and disease. For that, we are all grateful. But even the best vaccines fail to protect some people some of the time. The clinical trial data from both the Pfizer/BioNTech and the Moderna shows they are around 95% effective, which means that 5% of those fully vaccinated are still at risk for infection even a short time following the complete dose, when the vaccines are thought to be maximally effective.

I have wondered what might account for that 5%. Does the vaccine fail to elicit protective antibodies or is can variants breakthrough and cause infection? Now thanks to the extensive vaccination program in Israel and diligent follow-up of those vaccinated, we have a glimpse of the answer.

Israel is a world leader in vaccinating its population against Covid-19. As of the first week in April, approximately 80% of the adult population of Israel has been vaccinated. Almost all have received the mRNA Covid-19 vaccine developed by Pfizer/BioNTech. That has afforded Israeli scientists the opportunity to carefully examine those infected—as judged by detection of viral RNA by PCR analysis—beween the first and second vaccine dose and after receiving the full two doses of the vaccine. In each case, they determined the full-length sequence of each viral genome. The results of the study are available in an unreviewed preprint posted on MedRxiv, April 9, titled Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals.

The most significant finding was an enrichment of virus sequences corresponding to the B1.351 (South African) variant, as compared to the wild-type virus. Simultaneous measurements of the frequency of infection in carefully matched unvaccinated control populations allowed the scientists to calculate that the vaccine was eight times more protective against the wild type than the B1.351 variant. Similar studies showed that the vaccine is about 2.5 times more effective against the wild type than it is against the B 1.1.7 (UK) variant. The authors caution that although the direction of the protective effect against the three types of virus is clear, the actual magnitude of the difference is only approximate due to the limited number of breakthrough cases.

In seeking to explain their observations the authors write, “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”.

In commenting on their findings Adi Stern of Tel Aviv University was quoted as saying “We found a disproportionately higher rate of the South African variant among people vaccinated with a second dose, compared to the unvaccinated group. This means that the South African variant is able, to some extent, to break through the vaccine’s protection.”

The authors conclude by writing, “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 [variants of concern].”

 At present, there are several other variants of concern now circulating in the global population. Many of these variants are resistant, to one degree or another, to neutralizing antibodies present in the plasma of those who recover from infection by the original virus. Many of the variants also appear to be more infectious as judged by a rapid increase in prevalence in the population. The challenges of vaccine-resistant and highly resistant vaccines are not insurmountable but they are formidable, and as I’ve written about in Variants! The Shape-Shifting Challenge of COVID-19. It is urgent that we obtain real-world data on the protective effect of current vaccines against the full array of variants of concern.