New Study Suggests COVID-19 Vaccines Could be Approved Based on Antibody Levels Induced – Before Phase 3 Trials Are Finished

Levels of neutralizing antibodies in vaccinated individuals is a strong indicator of COVID-19 vaccine success- and this knowledge could be used to jump-start vaccine approvals and mass administration – even before large Phase 3 clinical trials are completed, suggests a new study by the University of Oxford Vaccine Group, Public Health England, and AstraZeneca

Knowledge of immune biomarkers could allow new vaccines to be authorised only with immunogenicity and safety data, and even before costly and time-consuming large scale efficacy trials are completed, the study published on the preprint server,, suggests. 

So using antibody biomarkers to further accelerate vaccine approvals could still help meet the huge unmet global demand that still exists, the study authors concluded, suggesting a bold new approach to vaccine approvals.  

“Understanding the relationship between immune responses to vaccines and protection against clinical outcomes is urgently needed to speed up vaccine development,” the researchers observed.

“The power of a correlate in vaccines is profound,” said Dan Barouch, Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, who authored an independent commentary in Nature on the new research.  

“If there’s a reliable correlate, then it can be used in clinical trials to make decisions as to what vaccines are likely to work, what form of vaccines are likely to work, or how durable the vaccines are going to be,” said Barouch. 

Even so, the science of antibody response is uneven, even with respect to the same vaccine.

“The probability of infection decreases on average with higher immune responses, but substantial variation exists between individuals,” acknowledged the authors.   

Eight vaccines have so far been recommended for use by the World Health Organization (WHO) – including the addition of two Chinese-made vaccines in June. Despite a vastly accelerated R&D timeline, approvals of other COVID vaccines in the pipeline still require many months as large-scale Phase 3 trials demonstrating efficacy must be completed. 

Study Vaccines Approved by WHO – More In Pipeline Now

Adjusted risk of primary symptomatic COVID-19 as a function of immune markers measured 28 days post second dose.
Top left: Anti-Spike IgG 28 days post boost Top right: Anti-RBD IgG 28 days post boost Bottom left: pseudovirus neutralisation antibody titres 28 days post boost
Bottom right: live neutralisation antibody titres 28 days post boost.
Grey lines show control (MenACWY) overall risk and vaccine (ChAdOx1 nCoV-19) overall risk. Blue dots show the absolute risk predicted from the model across the range of antibody values included in the analysis, adjusting for baseline exposure risk to SARS-CoV-2 infection (logit-transformed linear covariate including age, ethnicity, BMI, co-morbidities and healthcare worker status). Green shaded areas show the confidence interval around the predicted mean probability (green line) 

The Oxford and AstraZeneca study compared the immune responses of 171 vaccinated people who developed symptomatic infections to 1,404 vaccinated participants without a SARS-CoV2 infection, comparing four key biomarkers of antibody levels. 

Participants with higher levels of neutralizing antibodies tended to have stronger, although not complete protection from a symptomatic infection, the study found.

The risk of symptomatic COVID decreased with increasing levels of the following biomarkers of neutralizing antibodies: anti-spike immunoglobulin G (IgG), anti-receptor binding domain (RBD) IgG, pseudovirus neutralization titre, and live neutralization titre.  Immunoglobulin G antibodies are the basis of long-term protection.

“Finding the correlate of protection has really been a holy grail for this disease, as for others,” said Daniel Altmann, Professor of Immunology at Imperial College in a Nature commentary. “It’s surprisingly hard to do.” 

At the same time, while the antibody responses documented in the study proved to be a strong predictor for the development of symptomatic COVID infections, that was not at all the case for vaccine efficacy in terms of preventing asymptomatic infections. 

“Antibody responses did not correlate with overall protection against asymptomatic infection,” said the authors – meaning that the drivers of asymptomatic infections continue to elude researchers. 

Earlier Study Found Pfizer & Moderna Vaccines Produced More Neutralizing Antibodies that Other Vaccines 

Other studies have also demonstrated that vaccine-induced antibody levels are higher with some vaccines than others – explaining why some vaccines achieve higher levels of over all efficacy. Notably, a study in late May found induced levels of neutralizing antiboides to be highest with Moderna and Pfizer vaccines, as compared with Johnson & Johnson and AstraZeneca. 

The mRNA vaccines generated the strongest neutralizing antibody responses, and as a result were more protective. Vaccines that induced a weaker response provided lower levels of protection, said the authors. 

In the study published in Nature, researchers found a link between participants’ antibody levels recorded in early-stage trials and vaccine efficacy results from late-stage trials. 

The study estimated that a vaccine would have an efficacy of 50%, even if it induced antibody levels 80% lower than what would be found in a person who recovered from COVID-19. 

“Even low antibody levels, lower than we thought, will probably see you through,” said Altmann. 

Image Credits: WHO PAHO, Medrxiv.

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