Across an American gay male community worried about catching monkeypox, one message suggests this is all temporary: A few months of sexual caution plus vaccination will usher in a care-free autumn."For your own safety, and to spare you the horrors of this disease," sex columnist Dan Savage suggested on Twitter last weekend, "you might wanna think about maybe dialing it back for a few weeks while we roll the vaccine out." The AIDS magazine POZ recommends that readers "hold off on a slutty summer" and wait for the fall, when "we hope to have enough Jynneos vaccines for all who want it."Yet no one knows how well the Jynneos vaccine will serve as a get-out-of-infection-free card.One number that's been unquestionably quoted by various media organizations -- "85% effective" or "at least 85% effective" -- is based entirely on a small study done in Africa in the 1980s that has major limitations. One data expert calls its findings "pretty weak." Other studies have only been conducted in animals.Still, "I've heard from many folks in the community that they expect almost no risk of becoming infected 2 weeks after their first shot," said Michael Donnelly, MSc, a New York City data scientist and LGBT health advocate, in an interview with MedPage Today. "Or they think they won't get any symptoms if they were exposed before their shot."The lack of accurate information about the vaccine is "a big problem," Jay Varma, MD, director of the Cornell Center for Pandemic Prevention and Response in New York, said in an interview. "It is absolutely critical that public health officials work on messaging this uncertainty to people being vaccinated."Vaccine Assumptions Based on Small, 'Weak' 1988 StudyAs of July 29, the CDC reports that the current outbreak has caused 5,189 infections in the U.S., striking nearly every state (all except Montana, Wyoming, and Vermont) plus Puerto Rico. New York is by far the most affected with 1,345 cases, followed by California with 799, Illinois with 419, Florida with 373, and Texas and Georgia with 351 apiece. There's an especially high per-capita rate in Washington D.C., with 218 cases in a city of 702,000 people.Men who have sex with men are considered most vulnerable -- they made up 98% of 528 worldwide cases in a recent analysis -- and many gay men have gone onto social media or spoken to reporters to describe intense pain, horrific lesions, and barriers to care.Hundreds of thousands of Jynneos smallpox/monkeypox vaccines are now available in the U.S., and the CDC recommends vaccination for those who have been exposed to monkeypox or are at higher risk.Health officials prefer the Jynneos vaccine, which is manufactured by the Danish company Bavarian Nordic and FDA-approved to prevent both smallpox and monkeypox. An alternative vaccine, ACAM2000, is complicated to administer, produces a nasty and infectious pustule, and can cause side effects in some people such as those with weakened immune systems, according to Vox.As the CDC notes, "no data are available yet on the effectiveness of these vaccines in the current outbreak." As for previous outbreaks, only one study -- a retrospective analysis published in 1988 -- has examined whether a smallpox vaccine could prevent monkeypox.In that study, researchers tracked the household contacts of 209 people infected with monkeypox in Zaire in the early 1980s. Those with scars from previous smallpox vaccination (70%) were 85% less likely to be infected. The vaccine seemed to be 89% effective at protecting contacts outside the household from infection.The statistical analysis is limited since it has no confidence interval or adjustment for factors such as age, Ira Longini, PhD, a biostatistician at the University of Florida, told MedPage Today. Also, he said, the data are purely based on physical signs of vaccination. The study "is the only shred of evidence we have [in regard to vaccine effectiveness], which is pretty weak. In principle it should work, but we don't know."Jynneos and ACAM2000 are newer generations of vaccines such as Dryvax that were used in the 1980s. "These vaccines have not been tested directly against smallpox or monkeypox," said Richard Kennedy, PhD, co-director of the Mayo Vaccine Research Group in Rochester, Minnesota, in an interview with MedPage Today. "The immune responses they create are very close to first- or second-generation vaccines: A little weaker, but not much."Kennedy added that the vaccines also have been tested against monkeypox in five to 10 different animal studies. "These data are also clear and consistent with very good protection against disease with animals showing very few or no symptoms of illness after challenge," Kennedy said. "The animal data was strong enough that the FDA approved Jynneos to be licensed for prevention of monkeypox."Unique Outbreak May Weaken Vaccine's EffectsTo make matters more complicated, the new outbreak is quite different from those in the past. This time, the virus appears to largely be transmitted through sexual rather than other kinds of contact, with an overwhelming majority of cases among men who have sex with men. (There's now a debate in the medical world over whether to refer to monkeypox as a sexually transmitted disease [STD].) Previous outbreaks in Africa appeared to have been spread in households by various routes."The vaccine was evaluated on the assumption that most or all exposures would be from skin-to-skin contact," Varma told MedPage Today. "The head of the penis and interior of the anus may have characteristics that make them more susceptible to infection such as a lower dose of virus needed, less abundant antibodies or other components of the immune system, or concurrent STDs increasing risk. It's possible that the level of protection may be the same, but we should not assume it's the same without evaluating it."Also, he said, "it is theoretically possible for a monkeypox virus to develop mutations that make it more contagious or virulent to humans. The scientific consensus is that this is less likely to happen as quickly as happens with COVID, given the type of virus. COVID is an RNA virus, and monkeypox is a DNA virus."Kennedy agreed. "The current outbreak is caused by a strain that has a few genetic differences but is still very close to the strains causing monkeypox in the 1980s," he said. "This isn't like COVID-19 where you have a new strain with substantial immune evasion every few months. There is a lot of cross-protection with poxviruses -- an immune response to one poxvirus can recognize most other poxviruses."Fine-Tuning a Monkeypox Prevention MessageDespite the weakness of the evidence, the 85% efficacy number is everywhere -- sometimes with qualifications, sometimes not. Even Yale University and Harvard University have published health alerts that quote the 85% figure without noting its uncertainty.Meanwhile, monkeypox prevention messages aimed at gay and bisexual men continue to vary. Vaccinations are heavily touted along with other strategies as officials worry about stigmatizing gay men.Last week, the head of the World Health Organization suggested "reducing your number of sexual partners, reconsidering considering sex with new partners, and exchanging contact details with any new partners to enable follow up if needed."The CDC offered advice about having sex if someone may be infected: stay 6 feet apart during mutual masturbation and avoid kissing. And the magazine POZ suggests using condoms, wearing more clothes at circuit parties and bars, and creating sex "pods" similar to the groups of friends and relatives who only socialized with each other during the COVID-19 pandemic.Suggestions about condoms may be especially challenging for men who have sex with men to accept. Many gay men prefer to reduce their risk of HIV transmission by taking preventive drugs like emtricitabine/tenofovir (Descovy, Truvada) or, if they are HIV-positive, by lowering their viral loads to undetectable levels via medication."The prevention messaging should be that vaccinations will be an essential part of getting this outbreak under control, and we need everyone to get vaccinated as soon as possible," said Donnelly, the data scientist and LGBT health advocate. "But even if you're vaccinated, you're still at risk, and unprotected anal sex may be the highest risk.""Even after vaccination," he added, "you may want to consider reducing the number of your sex partners and using condoms or pursuing other safer sex approaches."Comment