vaccine rollout: 5 things that dictate success or failure

as a viral immunologist who develops immunization strategies to prevent infectious diseases and treat cancers, i would like to highlight outstanding questions about the emergency use of vaccines against  sars-cov-2 , the coronavirus that causes  covid-19 .

these vaccines have raised hopes that the pandemic is  nearing an end . hopefully this is true, but here are some potential sticking points.

short-term safety of approved covid-19 vaccines  looks   good . however, induction of  anaphylactic reactions  in  some vaccine recipients  hasn’t helped the optics for those with  vaccine hesitancy . but these cases are rare and usually associated with pre-existing severe allergies.

twenty-three frail elderly  individuals in norway  died shortly after receiving the pfizer vaccine . it is difficult to ascertain the reason for these deaths and they may have had nothing to do with the vaccine. it has put pressure on physicians in that country to try to determine which members of this demographic at high risk for covid-19 mortality should and should not be vaccinated.

duration of immunity  refers to how long a person is protected after being vaccinated. for previous vaccines, we could have reasonable confidence that immunity would last at least a few years prior to public rollouts. covid-19 vaccines only have a few months’ worth of  data on duration of immunity .

if  immunity declines  before “ herd immunity ” is achieved, previously vaccinated individuals will become susceptible to infection again and the rollout could fail.

there were public declarations of greater than 90 per cent effectiveness for the  moderna  and  pfizer  vaccines. unfortunately, pfizer did not publicly disclose the fact that there were large numbers of suspected, but unconfirmed cases of covid-19 that were excluded from their calculation of efficacy. this was revealed in a  summary report  issued by the united states food and drug administration (fda).

re-analysis of the data with this new information accounted for was performed by the associate editor of the  british medical journal , who reported his non-peer-reviewed findings in the journal’s opinion column. his estimate suggests the true effectiveness of the vaccine might be as low as  19 to 29 per cent . this can’t be confirmed or refuted until raw data not included in the fda report are released.

the effectiveness reported for sinovac biotech’s currently unapproved vaccine  dropped from 78 per cent  early in a clinical trial being run in brazil to  50.38  per cent in the late stages of the trial. the cut-off for approval of covid-19 vaccines has been set at  50 per cent effectiveness . if efficacy during public rollouts ends up being less than “advertised,” covid-19 vaccines will under-perform relative to expectations.

several   novel   variants  of sars-cov-2 have been identified recently. coronaviruses copy their genetic material in a way that inherently  induces random mutations . if these mutations promote survival of the virus in vaccinated people, it could spell disaster for the current immunization strategy.

although the risk of mutations that can evade vaccine-induced immunity cannot be accurately quantified, the way covid-19 vaccines are being rolled out will likely increase the potential for this to occur for at least two reasons. first, the current vaccines confer narrowly focused immunity that targets a single  viral spike protein . that means sars-cov-2 only needs to mutate one protein to evade vaccine-induced immunity. in contrast, it would be more difficult for the virus if it had to mutate several proteins to become immune-evasive.

secondly, the  vaccination program  is being rolled out in piece-meal fashion. this slow expansion of narrowly focused immunity among people who are surrounded by others who are not immune provides the time and contact with a “reservoir population” that a virus would need to generate random variants that can probe their potential to infect vaccinated people.

due to logistical challenges of rolling out two-shot vaccines and with the goal of maximizing how many and how quickly people can be vaccinated,  single-dose  regimens, combining  vaccines from different manufacturers , and regimens that alter the  intervals between doses  are all being considered.

note that the efficacy of pfizer’s and moderna’s vaccines only holds true beginning one to two weeks after the second shot, and using the recommended interval and dose. the performance of vaccines cannot be guaranteed if administered differently than the way in which they obtained regulatory approval. indeed, results of a single-dose regimen with the pfizer vaccine in israel were  reported as disappointing , although this is being debated.

the overall magnitude and/or quality of immune responses could be compromised by lengthening the interval between the two doses. deviations in protocols  should not be tolerated  unless backed up by clinical trial data.

can herd immunity still be achieved if covid-19 vaccines underperform? probably! mounting evidence suggests most people that have been infected with sars-cov-2 have  naturally acquired immunity  that can  protect them from re-infection . in fact, we have much longer duration data for naturally acquired immunity than for vaccine-induced immunity against sars-cov-2.

there is even evidence that pre-existing immunity against other coronaviruses, including those that merely cause colds, can  cross-protect  some people against sars-cov-2. this is not surprising because this is what our immune system is designed to do. all these people will contribute to the acquisition of herd immunity.

statistics canada  is initiating a large-scale study to conduct antibody testing on randomly selected canadians. a smaller study by a  researcher at the university of toronto  was started in june 2020. data from these studies could be used to estimate how much natural immunity exists in the general population. however, looking only for circulating antibodies against sars-cov-2 will likely underestimate immunity. these will often disappear, but the memory b cells that produce them  are usually long-lasting  and can  confer protection .