Waning immunity to Covid-19 – Expert Reaction

Health officials are considering booster shots for Covid-19, in the wake of Israel’s decision to offer a third shot, and the US’s call to offer a booster to certain immune-compromised people.

What do we know about how Covid immunity declines over time, and what implications do booster shots pose for vaccine equity?

The SMC has rounded up expert views from NZ and overseas on this topic.

Dr Fran Priddy, Clinical Evaluation Director Malaghan Institute of Medical Research, Clinical Director Vaccine Alliance Aotearoa New Zealand – Ohu Kaupare Huaketo (VAANZ), comments:

“The key indicator to follow in determining if and when COVID-19 booster doses may be needed is the rate of severe disease or hospitalisation among those already vaccinated. While immune responses, such as antibody levels, do decrease over time, the primary goal of COVID-19 vaccination is to protect against hospitalisation and death. So far, most COVID-19 vaccines, and in particular the mRNA vaccines such as the Pfizer vaccine used in New Zealand, appear to be holding in terms of protection against severe disease or hospitalisation.

“However we are watching the data from countries such as the US and Israel, which vaccinated large numbers of people using primarily mRNA vaccines early in 2021, to see if that high protection will continue over many months, in the face of Delta, particularly for the elderly.

“The data from the US still shows high effectiveness in preventing hospitalisation and death due to Delta infection across all age groups. But some recent data from Israel suggests that hospitalisation rates may be increasing in the elderly who were vaccinated an average of six months ago. And elderly who received a third booster dose appeared to have lower rates of hospitalisation from COVID-19 than those who did not. This is concerning, and both countries have made the decision to give boosters. However, please remember both countries are in the midst of another wave with thousands of new cases every day – 150,000 daily in US and about 8000 daily in Israel. For New Zealand, more data would be helpful to make an informed decision on boosters.

“Right now the priority is to get as many people as possible in New Zealand vaccinated with their primary series, particularly focusing on groups at higher risk such as Māori, Pasifika and the elderly, and ensuring vaccination is accessible.

“Another priority is to consider global vaccination rates and contribute to global efforts for vaccine equity, such as COVAX, since variants are a global issue. No country can be isolated forever. New Zealand has actively supported these efforts globally – including in the Pacific region. If we begin to move more quickly on vaccinating all at a national level, and there is sufficient vaccine supply, it is not unrealistic to then also consider the need for boosters.”

Conflict of interest statement: Dr Priddy is Clinical Director of the Government-funded Vaccine Alliance Aotearoa New Zealand – Ohu Kaupare Huaketo, a partnership between the Malaghan Institute, the University of Otago and Victoria University of Wellington.

Comments from US experts gathered by SciLine (18 August):

Jesse L. Goodman, Professor of Medicine, Georgetown University, United States, comments:

“Right now, what’s driving this consideration of booster shots is two things: One, we’re seeing the levels of antibody that vaccinated patients have declined over time, which can sometimes signal a loss in protection. But number two, more important, we’re seeing that the protection against overall infections is also declining. What we’re not seeing yet, and remains in question, is whether this has an effect on the outcomes we’re really trying to prevent, which is hospitalization, severe disease, death. And so far vaccine protection against those more severe manifestations is holding up well.”

We really don’t know yet how often we might need repeat COVID shots. Even though the antibody levels have been waning, suggesting we may need boosters periodically, we don’t know that they correlate perfectly with protection from infection. Also, we can’t predict what new variants COVID may throw at us and whether that may necessitate periodic changes and revaccination. So right now, anyone who tells you they can answer that question really can’t do so.”

Conflict of interest: Dr. Goodman is an infectious diseases clinician and also conducts research and policy work on emerging infectious diseases. He was previously FDA chief scientist, and before that director of FDA’s Center for Biologics Evaluation and Research (CBER). He reports serving as a board member for GSK and for Intellia Therapeutics (for which he receives compensation), and as a board member for the US Pharmacopeia, and on the scientific advisory board for the International AIDS Vaccine Initiative (IAVI) (both volunteer positions).

Ali Ellebedy, Associate Professor, Pathology and Immunology, Washington University School of Medicine in St. Louis, United States, comments:

“The limited data sets shared by the vaccine manufacturers show that indeed a third shot substantially increases neutralizing serum antibody levels so the body can more effectively fight off the virus. However, these samples were collected within a month after that third shot, which would be the time antibody production is highest after a booster shot. Two main questions remain: First, how sustained is the increase in antibody levels? Ideally it would last six months or more. Second, would that third shot impact the spread of highly infectious variants, such as delta?

Should we expect regular or annual COVID-19 booster shots?

“That will largely depend on how the situation with the variants evolves. So far, I do not see a reason for a regular or annual shot.”

No conflict of interest

Dorry Segev, Professor of Surgery and Epidemiology and Director, Epidemiology Research Group in Organ Transplantation, Johns Hopkins University, United States, comments:

“Right now in terms of boosters what we have are the same vaccine over again. So if our immune system has decreased to the vaccine we got, we can give more vaccine and our immune response increases. Ultimately I think what will happen is the variants will change to the point where we need new formulations of the vaccine. And I expect that that will happen every one to two years where the booster will actually be a new vaccine formulation.

“I have little doubt that at least once a year we’re going to be getting boosters for this virus, either in the form of new vaccines that cover new variants or boosters that take our decreased immune response and help it regain some protection.”

Conflict of interest: I am the PI of an NIH-funded trial of booster doses in transplant patients that just launched this week.

Balazs Halmos, Professor of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, United States, comments: 

This comment is an extract.

“So far there have been somewhat limited data about booster shots—meaning an extra dose of the same or a different vaccine beyond the currently authorized vaccination schedule—but emerging evidence seems to suggest that they can strengthen or achieve immunity in patients who are immune suppressed and who generally have a lesser chance of mounting an immune response. This includes patients after a solid organ transplant, certain types of cancers, especially blood cancers, and certain types of cancer treatments that impair the immune system.

“Questions remain about whether booster shots work for all patients or if some patients have such a low chance to respond to the additional shots that they need other methods of protection, as well as whether a mix and match strategy might work better—meaning getting a different type of a booster vaccine than the original series.”

No conflict of interest

Comments gathered by the UK Science Media Centre on the ZOE COVID Study (25 August):

Prof Ian Jones, Professor of Virology, University of Reading, said:

“Waning immunity has been a concern since the start of the epidemic, based on data from the commonly circulating coronaviruses. To date however, the studies that have followed vaccination have been a bit more sanguine, suggesting the fall off in antibody titre may be slower than first supposed. This latest study confirms that a decline is happening, but it is not yet clear what this means for disease severity, the key aspect of protection afforded by the vaccines. Sterilizing immunity is not induced by any of the vaccines so the fact that infection still occurs is not surprising but the immunity that is generated, which includes the non-neutralizing antibodies and T-cells that are less tested for, ensures that disease is minimised. The worst-case scenario suggested is certainly possible, but a better-case scenario would be that, even at 50% protection from infection, protection from disease remains robust and hospital numbers remain manageable.

“The need for boosters still needs to be balanced with global vaccine distribution to populations where even a first shot will lower virus circulation, and with it the chance of future variants.”

No conflict of interest declared.

Dr Simon Clarke, Associate Professor in Cellular Microbiology, University of Reading, comments:

This comment is an extract.

“The claim that immunity levels will hit around 50% by Christmas is not based on any robust analysis of data, and seems more like a finger in the air prediction. Immunity is a complex process and we cannot assume people’s immunity will fade at a uniform rate over time.

“However other, more robust data from other studies shows that while double vaccinated individuals are well protected against infection, and even better protected against serious disease, their level of immunity differs between individuals, and does dissipate over time. This is a reminder that we cannot rely on vaccines alone to prevent the spread of Covid. Lessons from countries like Israel, where the majority of the population were vaccinated early in 2021, shows that a new wave of infections, driven by new more infectious variants, can still drive up infection rates quickly.”

No conflict of interest declared.

Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice, Immediate past Chair of the BMA Public Health Medicine Committee, said:

“The press release is disappointing. As far as I can tell, it refers only to effectiveness against (any) infection. It doesn’t go into detail in the press release itself – you’d have to read and understand the papers it links to – but I assume “infection” means “confirmed infection”, ie people who report having tested positive.

“There are various ways in which vaccines can or might be effective. They might prevent infection altogether (and thereby onward transmission); they can reduce the duration, and level, of infectiousness in people who, despite vaccination, become infected; and they can prevent minor symptomatic infection (cough/cold/headache), more serious flu-like illness not requiring hospitalisation, illness severe enough to require hospitalisation, illness severe enough to require critical care (ICU admission), and death.

“There is a world of difference between efficacy against, on the one hand, any infection and on the other hand, illness severe enough to require hospitalisation, critical care, or to cause death.

“I am disappointed that the press release failed to tease out these differences, to explain more clearly what it means by “infection risk reduction”, and to comment on effectiveness against different outcomes.”

Conflict of interest: “Dr English is on the editorial board of Vaccines Today: an unpaid, voluntary, position. While he is also a member of the BMA’s Public Health Medicine Committee, this comment is made in a personal capacity.”

Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:

“This latest analysis from the ZOE app study provides additional and valuable information on the effectiveness of the vaccines currently in use in the UK. In general the reported findings from the ZOE study are consistent with those from other recent reports such as the ONS Oxford University study. These findings can be summarised as that the Pfizer vaccine offers improved effectiveness over the AZ vaccine and for both vaccines there is a demonstrable decline in effectiveness over a very few months. These observations are not surprising and were predictable from several months back.

“One issue is how much of this decline is vaccine effectiveness is down to waning immunity and how much is due to the greater prevalence of the Delta variant which is known to be more resistant to prior immunity from vaccination.

“What is not clear from the ZOE press release is whether this decline in effectiveness is based on symptomatic illness or whether they have identified declining effectiveness against severe disease. As we have pointed out previously COVID can be thought of as two phases of infection. The first phase is infection of the nose and throat (a mucosal infection) and we know that immunity to mucosal infections are rather short lived whether from vaccine or natural infection. Most cases of symptomatic covid are now these relatively mild mucosal infections. But it is these mucosal infections that are most likely to be associated with further transmission. The second phase a viral pneumonia which is more severe and is the illness that puts people into hospital. Immunity to these more severe (systemic) illnesses, are much more long lasting.

“This study adds further evidence that the effectiveness of vaccines against mild disease wanes after relatively few months and that this waning immunity is likely to be associated with reduced ability to reduce transmission. But as yet there is no strong evidence that immunity to severe disease wanes substantially over the same time scale or that vaccines are less effective at reducing the risk of severe disease from the delta as opposed to the alpha variants.”

No conflict of interest declared.